Publications by authors named "Lu-Ying Tang"

103 Publications

Liver involvement in patients with erythropoietic protoporphyria: retrospective analysis of clinicopathological features of 5 cases.

Ann Diagn Pathol 2022 Feb 17;56:151859. Epub 2021 Nov 17.

Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China. Electronic address:

Erythropoietic protoporphyria (EPP) is a rare inherited disease whose morbidity is about 1:75,000 to 1:200,000. It is caused by the deficiency of porphyrin ferrochelatase (FECH). Liver involvement in EPP is even rarer. The diagnosis of EPP with liver involvement mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing, which is still a huge challenge for both clinicians and pathologists. Here, 5 cases of EPP with liver injury were collected, and the clinicopathological features of these patients were analyzed. The clinical manifestations and laboratory examinations varied from person to person, whereas the liver biopsies showed that there were dark brown deposits within the hepatocytes, Kupffer cells, bile canaliculi and the lumen of bile ducts, which was a constant finding by histopathological examination. Gene tests were conducted in two of the five cases, and the results confirmed the diagnosis. Fully understanding of the diseases can help us reduce the rate of missed diagnosis and provide proper treatment as early as possible.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151859DOI Listing
February 2022

Identification of epigenetic modifications mediating the antagonistic effect of selenium against cadmium-induced breast carcinogenesis.

Environ Sci Pollut Res Int 2021 Nov 13. Epub 2021 Nov 13.

School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.

The antagonistic effect of selenium (Se) against cadmium (Cd)-induced breast carcinogenesis was reported, but underlying mechanisms were unclear. The aim of this study was to identify the epigenetically regulated genes and biological pathways mediating the antagonistic effect. We exposed MCF-7 cells to Cd and Se alone or simultaneously. Cell proliferation was assessed by MTT assay, and differential epigenome (DNA methylation, microRNA, and long non-coding RNA) was obtained by microarrays. We cross-verified the epigenetic markers with differential transcriptome, and the ones modulated by Cd and Se in opposite directions were regarded to mediate the antagonistic effect. The epigenetically regulated genes were validated by using gene expression data in human breast tissues. We further assessed the biological functions of these validated genes. Our results showed that Se alleviated the proliferative effect of Cd on MCF-7 cell. A total of 10 epigenetically regulated genes were regarded to mediate the antagonistic effect, including APBA2, KIAA0895, DHX35, CPEB3, SVIL, MYLK, ZFYVE28, ABLIM2, GRB10, and PCDH9. Biological function analyses suggested that these epigenetically regulated genes were involved in multiple cancer-related pathways, such as focal adhesion and PI3K/Akt pathway. In conclusion, we provided evidence that Se antagonized the Cd-induced breast carcinogenesis via epigenetic modification and revealed the critical pathways.
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http://dx.doi.org/10.1007/s11356-021-17355-zDOI Listing
November 2021

PIN3-mediated auxin transport contributes to blue light-induced adventitious root formation in Arabidopsis.

Plant Sci 2021 Nov 28;312:111044. Epub 2021 Aug 28.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China. Electronic address:

Adventitious rooting is a heritable quantitative trait that is influenced by multiple endogenous and exogenous factors in plants, and one important environmental factor required for efficient adventitious root formation is light signaling. However, the physiological significance and molecular mechanism of light underlying adventitious root formation are still largely unexplored. Here, we report that blue light-induced adventitious root formation is regulated by PIN-FORMED3 (PIN3)-mediated auxin transport in Arabidopsis. Adventitious root formation is significantly impaired in the loss-of-function mutants of the blue light receptors, PHOTOROPIN1 (PHOT1) and PHOTOROPIN2 (PHOT2), as well as the phototropic transducer, NON-PHOTOTROPIC HYPOCOTYL3 (NPH3). In addition, blue light enhanced the auxin content in the adventitious root, and the pin3 loss-of-function mutant had a reduced adventitious rooting response under blue light compared to the wild type. The PIN3 protein level was higher in plants treated with blue light than in those in darkness, especially in the hypocotyl pericycle, while PIN3-GFP failed to accumulate in nph3 PIN3::PIN3-GFP. Furthermore, the results showed that PIN3 physically interacted with NPH3, a key transducer in phototropic signaling. Taken together, our study demonstrates that blue light induces adventitious root formation through the phototropic signal transducer, NPH3, which regulates adventitious root formation by affecting PIN3-mediated auxin transport.
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http://dx.doi.org/10.1016/j.plantsci.2021.111044DOI Listing
November 2021

Prognostic value of glutaminase 1 in breast cancer depends on H3K27me3 expression and menopausal status.

Virchows Arch 2021 Sep 25. Epub 2021 Sep 25.

School of Public Health, Sun Yat-Sen University, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China.

Glutaminase 1 (GLS) is a therapeutic target for breast cancer; although GLS inhibitors have been developed, only a few subjects responded well to the therapy. Considering that the expression of histone H3 lysine 27 trimethylation (H3K27me3) and menopausal status was closely linked to GLS, we examined the effects of H3K27me3 and menopausal status on GLS to breast cancer prognosis. Data for 962 women diagnosed with primary invasive breast cancer were analyzed. H3K27me3 and GLS expression in tumors were evaluated with tissue microarrays by immunohistochemistry. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival and progression-free survival were estimated using Cox regression models. Statistical interaction was assessed on multiplicative scale. There was a beneficial prognostic effect of GLS expression on overall survival for those with low H3K27me3 level (HR = 0.50, 95% CI: 0.20-1.28) but an adverse prognostic effect for those with high H3K27me3 level (HR = 3.90, 95% CI: 1.29-11.78) among premenopausal women, and the statistical interaction was significant (P = 0.003). Similar pattern was further observed for progression-free survival (HR = 0.44, 95% CI: 0.20-0.95 for low H3K27me3 level, HR = 1.35, 95% CI: 0.74-2.48 for high H3K27me3 level, P = 0.024). The statistical interaction did not occur among postmenopausal women. Our study showed that the prognostic effects of GLS on breast cancer correlated to the expression level of H3K27me3 and menopausal status, which would help optimize the medication strategies of GLS inhibitors.
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http://dx.doi.org/10.1007/s00428-021-03210-6DOI Listing
September 2021

Osmotic stress represses root growth by modulating the transcriptional regulation of PIN-FORMED3.

New Phytol 2021 11 8;232(4):1661-1673. Epub 2021 Sep 8.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430072, China.

Osmotic stress influences root system architecture, and polar auxin transport (PAT) is well established to regulate root growth and development. However, how PAT responds to osmotic stress at the molecular level remains poorly understood. In this study, we explored whether and how the auxin efflux carrier PIN-FORMED3 (PIN3) participates in osmotic stress-induced root growth inhibition in Arabidopsis (Arabidopsis thaliana). We observed that osmotic stress induces a HD-ZIP II transcription factor-encoding gene HOMEODOMAIN ARABIDOPSIS THALIANA2 (HAT2) expression in roots. The hat2 loss-of-function mutant is less sensitive to osmotic stress in terms of root meristem growth. Consistent with this phenotype, whereas the auxin response is downregulated in wild-type roots under osmotic stress, the inhibition of auxin response by osmotic stress was alleviated in hat2 roots. Conversely, transgenic lines overexpressing HAT2 (Pro35S::HAT2) had shorter roots and reduced auxin accumulation compared with wild-type plants. PIN3 expression was significantly reduced in the Pro35S::HAT2 lines. We determined that osmotic stress-mediated repression of PIN3 was alleviated in the hat2 mutant because HAT2 normally binds to the promoter of PIN3 and inhibits its expression. Taken together, our data revealed that osmotic stress inhibits root growth via HAT2, which regulates auxin activity by directly repressing PIN3 transcription.
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http://dx.doi.org/10.1111/nph.17687DOI Listing
November 2021

Time-varying effects of FOXA1 on breast cancer prognosis.

Breast Cancer Res Treat 2021 Jun 18;187(3):867-875. Epub 2021 Feb 18.

School of Public Health, Sun Yat-Sen University, 74 Zhongshan 2nd Rd, Guangzhou, 510080, China.

Purpose: Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis.

Methods: FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan-Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1.

Results: Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271-285 of FOXA1 expression increased from 0.35 (95% CI 0.14-0.86) at 6 months after diagnosis to 2.88 (95% CI 1.35-6.15) at 120 months with a crossover at around 36 months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P < 0.01) and PFS (P = 0.01) but were attenuated for ER (P = 0.13 for OS).

Conclusions: This study revealed an independent time-varying effect of FOXA1 on breast cancer prognosis, which would provide an insight into the roles of FOXA1 as a marker of breast cancer prognosis and may help optimize the medication strategies.
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http://dx.doi.org/10.1007/s10549-021-06125-7DOI Listing
June 2021

The metabolite methylglyoxal-mediated gene expression is associated with histone methylglyoxalation.

Nucleic Acids Res 2021 02;49(4):1886-1899

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan 430072, China.

Methylglyoxal (MG) is a byproduct of glycolysis that functions in diverse mammalian developmental processes and diseases and in plant responses to various stresses, including salt stress. However, it is unknown whether MG-regulated gene expression is associated with an epigenetic modification. Here we report that MG methylglyoxalates H3 including H3K4 and increases chromatin accessibility, consistent with the result that H3 methylglyoxalation positively correlates with gene expression. Salt stress also increases H3 methylglyoxalation at salt stress responsive genes correlated to their higher expression. Following exposure to salt stress, salt stress responsive genes were expressed at higher levels in the Arabidopsis glyI2 mutant than in wild-type plants, but at lower levels in 35S::GLYI2 35S::GLYII4 plants, consistent with the higher and lower MG accumulation and H3 methylglyoxalation of target genes in glyI2 and 35S::GLYI2 35S::GLYII4, respectively. Further, ABI3 and MYC2, regulators of salt stress responsive genes, affect the distribution of H3 methylglyoxalation at salt stress responsive genes. Thus, MG functions as a histone-modifying group associated with gene expression that links glucose metabolism and epigenetic regulation.
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http://dx.doi.org/10.1093/nar/gkab014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913762PMC
February 2021

Differential epigenetic profiles induced by sodium selenite in breast cancer cells.

J Trace Elem Med Biol 2021 Mar 12;64:126677. Epub 2020 Nov 12.

School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Objectives: Selenium (Se) was a potential anticancer micronutrient with proposed epigenetic effect. However, the Se-induced epigenome in breast cancer cells was yet to be studied.

Methods: The profiles of DNA methylation, microRNA (miRNA), long non-coding RNA (lncRNA), and message RNA (mRNA) in breast cancer cells treated with sodium selenite were examined by microarrays. We verified the epigenetic modifications by integrating their predicted target genes and differentially expressed mRNAs. The epigenetically regulated genes were further validated in a breast cancer cohort by associating with tumor progression. We conducted a series of bioinformatics analyses to assess the biological function of these validated genes and identified the critical genes.

Results: The Se-induced epigenome regulated the expression of 959 genes, and 349 of them were further validated in the breast cancer cohort. Biological function analyses suggested that these validated genes were enriched in several cancer-related pathways, such as PI3K/Akt and metabolic pathways. Based on the degrees of expression change, hazard ratio difference, and connectivity, NEDD4L and FMO5 were identified as the critical genes.

Conclusions: These results confirmed the epigenetic effects of sodium selenite and revealed the epigenetic profiles in breast cancer cells, which would help understand the mechanisms of Se against breast cancer.
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http://dx.doi.org/10.1016/j.jtemb.2020.126677DOI Listing
March 2021

Differential epigenetic and transcriptional profile in MCF-7 breast cancer cells exposed to cadmium.

Chemosphere 2020 Dec 31;261:128148. Epub 2020 Aug 31.

School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

Cadmium (Cd) has been confirmed to be associated with breast carcinogenesis, but the mechanism was not clarified yet. Given that epigenetic modification was speculated as underlying mechanism, we examined the differential epigenome caused by Cd in breast cancer cells. Profiles of DNA methylation, microRNA (miRNA), long non-coding RNA (lncRNA), and message RNA (mRNA) were derived from Cd-treated and untreated MCF-7 breast cancer cells by microarray. We identified 997 target genes epigenetically regulated by Cd through cross-verification with the differential epigenome and transcriptome, and 400 of them were further validated in a breast cancer cohort. Biological function analyses suggested that several pathways were involved in Cd-induced breast carcinogenesis, such as Wnt signaling, metabolism, and human papilloma virus (HPV) infection. TXNRD1 and CCT3 were further identified as the critical genes based on the degree of expression change, hazard ratio difference, and connectivity. The present study revealed that Cd epigenetically regulated several pathways involving in breast carcinogenesis, particularly the Wnt signaling and metabolic pathways, among which TXNRD1 and CCT3 might play critical roles. It was also suggested that Cd and HPV infection might jointly participate in breast tumorigenesis.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128148DOI Listing
December 2020

WRKY13 Enhances Cadmium Tolerance by Promoting and Hydrogen Sulfide Production.

Plant Physiol 2020 05 16;183(1):345-357. Epub 2020 Mar 16.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan 430072, China

Hydrogen sulfide (HS), a plant gasotransmitter, functions in the plant response to cadmium (Cd) stress, implying a role for cysteine desulfhydrase in producing HS in this process. Whether () acts in the plant Cd response remains to be identified, and if it does, how is regulated in this process is also unknown. Here, we report that -mediated HS production enhances plant Cd tolerance in Arabidopsis (). When subjected to Cd stress, a mutant accumulated more Cd and reactive oxygen species and showed increased Cd sensitivity, whereas transgenic lines overexpressing had decreased Cd and reactive oxygen species levels and were more tolerant to Cd stress compared with wild-type plants. Furthermore, the expression of was stimulated by Cd stress, and this up-regulation was mediated by a Cd-induced transcription factor, WRKY13, which bound to the promoter. Consistently, the higher Cd sensitivity of the mutant was rescued by the overexpression of Together, our results demonstrate that Cd-induced WRKY13 activates expression to increase the production of HS, leading to higher Cd tolerance in plants.
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http://dx.doi.org/10.1104/pp.19.01504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210638PMC
May 2020

Associations of reproductive factors with breast cancer prognosis and the modifying effects of menopausal status.

Cancer Med 2020 01 14;9(1):385-393. Epub 2019 Nov 14.

School of Public Health, Sun Yat-sen University, Guangzhou, China.

Reproductive factors associated with breast cancer risk may also affect the prognosis. This study aimed to evaluate the associations of multiple reproductive factors with breast cancer prognosis and the modifying effects of menopausal status. We obtained data from 3805 breast cancer patients recruited between October 2008 and June 2016 in Guangzhou. The subjects were followed up until 30 June 2018. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using multivariate Cox models to estimate the associations. It was found that there were U-shaped patterns for the associations of age at first birth and durations from first/last birth to diagnosis with breast cancer prognosis. The adverse effects of old age at first birth [>30 years vs 23-30 years, HR (95% CI): 1.59 (1.01-2.50)] and long intervals from first [≥20 years vs 10-19 years, HR (95% CI): 1.55 (1.07-2.27)] or last [≥20 years vs 10-19 years, HR (95% CI): 1.63 (1.08-2.46)] birth to diagnosis on progression-free survival (PFS) were significantly more pronounced among premenopausal women. Additionally, long interval (>5 years) between first and second birth was associated with a better PFS [HR (95% CI): 0.64 (0.42-0.97)]. These results suggested that age at first birth, durations from first/last birth to diagnosis, and intervals between first and second birth should be taken into account when following the patients and assessing the prognosis of breast cancer, particularly for premenopausal patients. These findings would also have implications for further insight into the mechanisms of breast cancer development.
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http://dx.doi.org/10.1002/cam4.2707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943140PMC
January 2020

Auxin abolishes SHI-RELATED SEQUENCE5-mediated inhibition of lateral root development in Arabidopsis.

New Phytol 2020 01 12;225(1):297-309. Epub 2019 Sep 12.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Lateral roots (LRs), which form in the plant postembryonically, determine the architecture of the root system. While negative regulatory factors that inhibit LR formation and are counteracted by auxin exist in the pericycle, these factors have not been characterised. Here, we report that SHI-RELATED SEQUENCE5 (SRS5) is an intrinsic negative regulator of LR formation and that auxin signalling abolishes this inhibitory effect of SRS5. Whereas LR primordia (LRPs) and LRs were fewer and less dense in SRS5ox and Pro35S:SRS5-GFP plants than in the wild-type, they were more abundant and denser in the srs5-2 loss-of-function mutant. SRS5 inhibited LR formation by directly downregulating the expression of LATERAL ORGAN BOUNDARIES-DOMAIN 16 (LBD16) and LBD29. Auxin repressed SRS5 expression. Auxin-mediated repression of SRS5 expression was not observed in the arf7-1 arf19-1 double mutant, likely because ARF7 and ARF19 bind to the promoter of SRS5 and inhibit its expression in response to auxin. Taken together, our data reveal that SRS5 negatively regulates LR formation by repressing the expression of LBD16 and LBD29 and that auxin releases this inhibitory effect through ARF7 and ARF19.
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http://dx.doi.org/10.1111/nph.16115DOI Listing
January 2020

Effects of tea consumption and the interactions with lipids on breast cancer survival.

Breast Cancer Res Treat 2019 Aug 16;176(3):679-686. Epub 2019 May 16.

School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, China.

Purpose: The effect of tea consumption on breast cancer survival remained to be explored. Meanwhile, green tea favorably facilitates lipid metabolisms in breast cancer survivors. This study aimed to examine the effect of tea consumption and the interactions with lipids on breast cancer survival.

Methods: A total of 1551 breast cancer patients were recruited between April 2008 and March 2012 and followed up until 31 December 2017 in Guangzhou. The endpoint was progression-free survival (PFS). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox proportional to estimate the associations.

Results: PFS was better among women who regularly drank all teas (mainly green tea) except oolong after cancer diagnosis compared with non-tea drinkers (HR 0.52; 95% CI 0.29 ~ 0.91). This association was more evident among women with normal (HR 0.38; 95% CI 0.18 ~ 0.82) than higher (HR 1.22; 95% CI 0.13 ~ 11.82) total cholesterol, though the interaction was not significant. Moreover, the more they drank (≥ 7 times/week), the better prognosis was (HR 0.30; 95% CI 0.11 ~ 0.84). In contrast, oolong tea was observed to have a potential impaired effect on PFS.

Conclusions: Our findings suggested that regularly drinking all teas (mainly green tea) except oolong after diagnosis was beneficial to breast cancer survival, particularly for women with normal lipids, while oolong tea may have an impaired effect.
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http://dx.doi.org/10.1007/s10549-019-05253-5DOI Listing
August 2019

Joint effects of multiple sleep characteristics on breast cancer progression by menopausal status.

Sleep Med 2019 02 12;54:153-158. Epub 2018 Nov 12.

School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Objectives: Sleep has been closely linked to breast cancer risk. However, the association between sleep and breast cancer prognosis remains unclear. The aim of this study was to evaluate the separate and joint effects of multiple sleep characteristics on breast cancer prognosis among Chinese women.

Methods: A total of 1580 breast cancer patients were recruited between October 2008 and December 2014 and followed up until December 31, 2017 in Guangzhou. Multivariate Cox models were conducted to estimate the hazard ratios (HR) and 95% confidence intervals (95%CI) for breast cancer prognosis in association with sleep characteristics.

Results: Long sleep duration at night (>9 h) (HR = 2.33, 95%CI: 1.01-5.42), poor sleep quality (HR = 3.08, 95%CI: 1.74-5.47), and impaired daytime function (HR = 2.49, 95%CI: 1.65-3.79) after diagnosis were associated with an increased risk of breast cancer progression. Both short sleep duration (<6 h) (HR = 2.00, 95%CI: 1.06-3.77, P = 0.011) and long sleep duration (>9 h) (HR = 4.69, 95%CI: 1.31-16.78, P = 0.187) increased the progression risk only among patients with impaired but not normal daytime function. In addition, daytime napping significantly modified the effect of short sleep duration on the progression (HR = 3.55, 0.59, 95%CI: 1.55-7.97, 0.23-1.53 for patients without and with daytime napping, respectively, P = 0.005). Stratification results suggested that the associations were more evident among pre-menopausal patients, although no significant interaction was observed.

Conclusion: Our findings suggested that inadequate sleep duration to feel one's best and poor sleep quality after diagnosis were associated with an increased risk of breast cancer progression, particularly for pre-menopausal women.
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http://dx.doi.org/10.1016/j.sleep.2018.10.025DOI Listing
February 2019

SORTING NEXIN 1 Functions in Plant Salt Stress Tolerance Through Changes of NO Accumulation by Regulating NO Synthase-Like Activity.

Front Plant Sci 2018 6;9:1634. Epub 2018 Nov 6.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, China.

Nitric oxide (NO) production via NO synthase (NOS) plays a vital role in plant tolerance to salt stress. However, the factor(s) regulating NOS-like activity in plant salt stress tolerance remains elusive. Here, we show that (), which can restore HO-induced NO accumulation in yeast Δ mutant, functions in plant salt stress tolerance. Salt stress induced NO accumulation through promoted NOS-like activity in the wild type, but this induction was repressed in salt-stressed mutant with the mutation of because NOS-like activity was inhibited in the mutant. Consistently, displayed reduced tolerance to high salinity with decreased survival rate compared with the wild type, and exogenous treatment with NO donor significantly rescued the hypersensitivity of the mutant to salt stress. In addition, the mutant with reduced NOS-like activity repressed the expression of stress-responsive genes, decreased proline accumulation and anti-oxidant ability compared with wild-type plants when subjected to salt stress. Taken together with our finding that salt induces the expression of SNX1, our results reveal that SNX1 plays a crucial role in plant salt stress tolerance by regulating NOS-like activity and thus NO accumulation.
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http://dx.doi.org/10.3389/fpls.2018.01634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277890PMC
November 2018

Patient and Care Delays of Breast Cancer in China.

Cancer Res Treat 2019 Jul 6;51(3):1098-1106. Epub 2018 Nov 6.

Department of Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Purpose: This study differentiates patient and care delays of breast cancer and explores the related factors as well as the associations with the prognosis in Guangzhou, a southern city of China.

Methods: A cohort of female incident breast cancer patients (n=1,551) was recruited from October 2008 to March 2012 and followed up until January 1, 2016 (n=1,374) in the affiliated hospitals of Sun Yat-sen University. The factors associated with patient and care delays were analyzed with multivariable logistic models. Cox proportional hazards regression models were constructed to estimate the impacts of the delays on the prognosis.

Results: There were 40.4% patient delay (≥3 months) and 15.5% care delay (≥1 month). The patient delay, but not the care delay, was significantly related to the clinical stage and consequently worsened the prognosis of breast cancer (hazard ratio, 1.45; 95% confidence interval, 1.09 to 1.91 for progression-free survival). The factors related to an increased patient delay included premenopausal status, history of benign breast disease, and less physical examination.

Conclusion: Patient delay was the main type of delay in Guangzhou and resulted in higher clinical stage and poor prognosis of breast cancer. Screening for breast cancer among premenopausal women may be an effective way to reduce this delay.
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http://dx.doi.org/10.4143/crt.2018.386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639234PMC
July 2019

General control non-repressible 20 (GCN20) functions in root growth by modulating DNA damage repair in Arabidopsis.

BMC Plant Biol 2018 Nov 12;18(1):274. Epub 2018 Nov 12.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Background: Most ABC transporters are engaged in transport of various compounds, but its subfamily F lacks transmembrane domain essential for chemical transportation. Thus the function of subfamily F remains further elusive.

Results: Here, we identified General Control Non-Repressible 20 (GCN20), a member of subfamily F, as new factor for DNA damage repair in root growth. While gcn20-1 mutant had a short primary root with reduced meristem size and cell number, similar primary root lengths were assayed in both wild-type and GCN20::GCN20 gcn20-1 plants, indicating the involvement of GCN20 in root elongation. Further experiments with EdU incorporation and comet assay demonstrated that gcn20-1 displays increased cell cycle arrest at G2/M checkpoint and accumulates more damaged DNA. This is possible due to impaired ability of DNA repair in gcn20-1 since gcn20-1 seedlings are hypersensitive to DNA damage inducers MMC and MMS compared with the wild type plants. This note was further supported by the observation that gcn20-1 is more sensitive than the wild type when subjected to UV treatment in term of changes of both fresh weight and survival rate.

Conclusions: Our study indicates that GCN20 functions in primary root growth by modulating DNA damage repair in Arabidopsis. Our study will be useful to understand the functions of non-transporter ABC proteins in plant growth.
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http://dx.doi.org/10.1186/s12870-018-1444-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233562PMC
November 2018

Decelerated DNA methylation age predicts poor prognosis of breast cancer.

BMC Cancer 2018 Oct 17;18(1):989. Epub 2018 Oct 17.

The School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China.

Background: DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of breast cancer.

Methods: We retrieved information of 1076 breast cancer patients from Genomic Data Commons (GDC) data portal on March 30, 2017, including breast cancer DNAm profiling, demographic features, clinicopathological parameters, recurrence, and all-cause fatality. Horvath's method was applied to calculate the DNAm age. Cox proportional hazards regression models were used to test the associations between DNAm age of the cancerous tissues and the prognosis (recurrence of breast cancer and all-cause fatality) with or without adjusting for chronological age and clinicopathological parameters.

Results: The DNAm age was markedly decelerated in the patients who were premenopausal, ER or PR negative, HER2-enriched or basal-like than their counterparts. In the first five-year follow-up dataset for survival, every ten-year increase in DNAm age was associated with a 15% decrease in fatality; subjects with DNAm age in the second (HR: 0.52; 95%CI: 0.29-0.92), the third (HR: 0.49; 95%CI: 0.27-0.87) and the fourth quartile (HR: 0.38; 95%CI: 0.20-0.72) had significant longer survival time than those in the first quartile. In the first five-year follow-up dataset for recurrence, every ten-year increase in DNAm age was associated with a 14% decrease of the recurrence; in the categorical analysis, a clear dose-response was shown (P for trend =0.02) and the fourth quartile was associated with a longer recurrence free survival (HR: 0.32; 95%CI: 0.14-0.74). In the full follow-up dataset, similar results were obtained.

Conclusions: DNAm age of breast cancer tissue, which associated with menopausal status and pathological features, was a strong independent predictor of the prognosis. It was suggested that the prognosis of breast cancer was related to intrinsic biological changes and specific molecular targets for treatment of breast cancer may be implicit.
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http://dx.doi.org/10.1186/s12885-018-4884-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191915PMC
October 2018

The COP1 Target SHI-RELATED SEQUENCE5 Directly Activates Photomorphogenesis-Promoting Genes.

Plant Cell 2018 10 27;30(10):2368-2382. Epub 2018 Aug 27.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan 430072, China

Plant seedlings undergo distinct developmental processes in the dark and in the light. Several genes, including (), (), and , have been identified as photomorphogenesis-promoting factors in ; however, the overexpression of these genes does not induce photomorphogenesis in the dark. Using an activation-tagging approach, we identified , which overexpresses () following induction with estradiol. overexpression in and seedlings results in a constitutive photomorphogenesis phenotype in the dark, whereas loss of function in the mutant results in long hypocotyls in the light. This indicates that SRS5 is a positive regulator of photomorphogenesis. Furthermore, SRS5 promotes photomorphogenesis by directly binding to the promoters of photomorphogenesis-promoting genes, such as , , and , and activating their expression, thus affecting the expression of downstream light-signaling genes. These data indicate that SRS5 acts in the upregulation of photomorphogenesis-promoting genes. In addition, CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), which plays a central repressive role in seedling photomorphogenesis, directly ubiquitinates SRS5, promoting its degradation in the dark. Taken together, our results demonstrate that SRS5 directly activates the expression of downstream genes , , and and is a target of COP1-mediated degradation in Arabidopsis.
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http://dx.doi.org/10.1105/tpc.18.00455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241259PMC
October 2018

Molecular features in young vs elderly breast cancer patients and the impacts on survival disparities by age at diagnosis.

Cancer Med 2018 May 15. Epub 2018 May 15.

The School of Public Health, Sun Yat-sen University, Guangzhou, China.

Young and elderly breast cancer patients are more likely to have a poorer outcome than middle-aged patients. The intrinsic molecular features for this disparity are unclear. We obtained data from the Cancer Genome Atlas (TCGA) on May 15, 2017 to test the potential mediation effects of the molecular features on the association between age and prognosis with a four-step approach. The relative contributions of the molecular features (PAM50 subtype, risk stratification, DNAm age, and mutations in TP53, PIK3CA, MLL3, CDH1, GATA3, and MAP3K1) to age disparities in survival were estimated by Cox proportional hazard models with or without the features. Young patients were significantly more likely to have basal-like subtype, GATA3 mutations, and younger DNA methylation (DNAm) age than middle-aged patients (P < .05). Both the young and elderly patients had a significantly increased risk of breast cancer recurrence after adjusted by race, tumor size, and node status (Hazard ratio [HR] (95% confidence interval [CI]): 2.81 [1.44, 5.45], 2.37 [1.45, 3.89], respectively). This increased risk was weakened in the young patients after further adjustments in the molecular features, particularly basal-like subtype, GATA3 mutations, and DNAm age (HR [95%CI]: 1.87 [0.81, 4.32]), resulting in 33.5% decreased risk of recurrence. Meanwhile, the adjustments of the molecular features did not alter the recurrence risk for the elderly patients. Compared with middle-aged patients of breast cancer, poorer prognosis of elderly patients may be caused by aging, while poorer prognosis of young patients was probably mediated through intrinsic characteristics, such as basal-like subtype, GATA3 mutations, and DNAm age of the cancerous tissues.
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http://dx.doi.org/10.1002/cam4.1544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051220PMC
May 2018

WD40-REPEAT 5a represses root meristem growth by suppressing auxin synthesis through changes of nitric oxide accumulation in Arabidopsis.

Plant J 2018 03 6;93(5):883-893. Epub 2018 Feb 6.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Although nitric oxide (NO) is known to regulate root growth, the factor(s) modulating NO during this process have not yet been elucidated. Here, we identified Arabidopsis WD40-REPEAT 5a (WDR5a) as a novel factor that functions in root growth by modulating NO accumulation. The wdr5a-1 mutant accumulated less NO and produced longer roots than the wild type, whereas the WDR5a overexpression lines had the opposite phenotype. The role of NO was further supported by our observation that the NO donor sodium nitroprusside (SNP) and the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) rescued the root meristem growth phenotypes of the wdr5a-1 and WDR5a overexpression lines, respectively. The regulation of root growth by WDR5a was found to involve auxin because the auxin levels were similar in SNP-treated wdr5a-1 and wild-type roots, but higher in untreated wdr5a-1 roots than in wild-type roots. In addition, the wdr5a-1 mutant had higher production and activity levels of the auxin biosynthetic enzyme TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS1 (TAA1), in contrast to its reduced expression and activity in the WDR5a overexpression lines, and the increased root meristem growth in wdr5a-1 was suppressed by treatment with l-kynurenine, which inhibits TAA1, as well as by mutating TAA1. WDR5a therefore functions in root meristem growth by maintaining NO homeostasis, and thus TAA1-mediated auxin biosynthesis.
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http://dx.doi.org/10.1111/tpj.13816DOI Listing
March 2018

Polymorphisms in homologous recombination repair genes and the risk and survival of breast cancer.

J Gene Med 2017 Sep 10;19(9-10). Epub 2017 Oct 10.

The School of Public Health, Sun Yat-sen University, Guangzhou, China.

Background: Immunoglobulin (Ig)A antibody of Epstein-Barr virus (EBV) was found to associate with breast cancer (BC), whereas IgA positivity was related to a series of genetic markers in the genes of homologous recombination repair system (HRRs). We assessed the associations of the polymorphisms in HRR genes with the risk and survival of BC.

Methods: A case-control study was conducted with 1551 bc cases and 1605 age-matched healthy controls between October 2008 and March 2012 in the Guangzhou Breast Cancer Study (GZBCS), China, and the case population were followed up until 31 January 2016. Five single nucleotide polymorphisms of candidate genes in HRR system were genotyped. Odds ratios (ORs) and hazards ratios (HRs) were calculated using multivariate logistic regression and Cox proportional hazards regression to estimate the risk and prognostic effect, respectively.

Results: RFC1 rs6829064 (AA) was associated with an increased BC risk [OR = 1.35; 95% confidence interval (CI) = 1.06-1.73] compared to the wild genotype (GG). NRM rs1075496 (GT/TT versus GG) was associated with a worse progression-free survival (PFS) and the HR was 1.34 (95% CI = 1.01-1.78), particularly among advanced patients. LIG3 rs1052536 (CT/TT versus CC) was associated with a better PFS and the HR was 0.70 (95% CI = 0.53-0.93). However, RAD54L rs1710286 and RPA1 rs11078676 were not observed to be associated with either the risk or survival of BC.

Conclusions: The findings of the present study suggest that the polymorphisms in HRR genes were associated with BC risk (RFC1 rs6829064) and prognosis (NRM rs1075496 and LIG3 rs1052536), whereas RAD54L rs1710286 and RPA1 rs11078676 had null associations with BC.
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http://dx.doi.org/10.1002/jgm.2988DOI Listing
September 2017

Associations of Epstein-Barr Virus DNA in PBMCs and the Subtypes with Breast Cancer Risk.

J Cancer 2017 25;8(15):2944-2949. Epub 2017 Aug 25.

School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.

Epstein-Barr virus (EBV) has been found to be implicated in the development of breast cancer. The purpose of the present study was to identify the associations of EBV DNA and the subtypes in peripheral blood mononuclear cells (PBMCs) with the risk of breast cancer. A case-control study with 671 breast cancer cases and 859 age-matched controls was conducted in Guangzhou, China. Face-to-face interviews were performed and blood samples were collected immediately after admission to the hospital for patients or after the interview for controls. EBV DNA in PBMCs and the subtypes were detected using Polymerase Chain Reaction (PCR) and restricted fragment length polymorphisms (RFLP). IgA antibodies against EBV VCA-p18 and EBNA-1 were examined using commercial enzyme-linked immunosorbent assay kits. Unconditional logistic regression analysis was applied to evaluate the associations of the DNA positivity and subtypes of EBV with the risk of breast cancer. Among the 1530 subjects, 164 cases (24.4 %) and 206 controls (24.0 %) were positive for EBV DNA in PBMCs and no significant difference occurred between cases and controls. The presence of EBV DNA was related to the positivity of EBV IgA antibodies. Of the DNA positive samples, 71 cases and 109 controls for F/f subtype and 58 cases and 112 controls for C/D subtype were successfully obtained. The D subtype was associated with an increased breast cancer risk compared with the C subtype [OR (95% CI): 2.86 (1.25~6.53)]. We did not find an association of the F/f polymorphism with breast cancer risk. The present study suggested that the presence of EBV DNA in PBMCs may not be an appropriate biomarker for breast cancer risk. The subtype D of EBV was likely to be related to breast tumorigenesis.
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http://dx.doi.org/10.7150/jca.20330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604445PMC
August 2017

CATALASE2 functions for seedling postgerminative growth by scavenging H O and stimulating ACX2/3 activity in Arabidopsis.

Plant Cell Environ 2017 Nov 21;40(11):2720-2728. Epub 2017 Sep 21.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Increased fatty acid β-oxidation is essential for early postgerminative growth in seedlings, but high levels of H O produced by β-oxidation can induce oxidative stress. Whether and how catalase (CAT) functions in fine-tuning H O homeostasis during seedling growth remain unclear. Here, we report that CAT2 functions in early seedling growth. Compared to the wild type, the cat2-1 mutant, with elevated H O levels, exhibited reduced root elongation on sucrose (Suc)-free medium, mimicking soils without exogenous sugar supply. Treatment with the H O scavenger potassium iodide rescued the mutant phenotype of cat2-1. In contrast to the wild type, the cat2-1 mutant was insensitive to the CAT inhibitor 3-amino-1,2,4-triazole in terms of root elongation when grown on Suc-free medium, suggesting that CAT2 modulates early seedling growth by altering H O accumulation. Furthermore, like cat2-1, the acyl-CoA oxidase (ACX) double mutant acx2-1 acx3-6 showed repressed root elongation, suggesting that CAT2 functions in early seedling growth by regulating ACX activity, as this activity was inhibited in cat2-1. Indeed, decreased ACX activity and short root of cat2-1 seedlings grown on Suc-free medium were rescued by overexpressing ACX3. Together, these findings suggest that CAT2 functions in early seedling growth by scavenging H O and stimulating ACX2/3 activity.
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http://dx.doi.org/10.1111/pce.13031DOI Listing
November 2017

Modification effects of genetic polymorphisms in FTO, IL-6, and HSPD1 on the associations of diabetes with breast cancer risk and survival.

PLoS One 2017 7;12(6):e0178850. Epub 2017 Jun 7.

Department of Statistics and Epidemiology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, School of Public Health, Sun Yat-Sen University, Guangzhou, China.

The contribution of diabetes to breast cancer remains uncertain among Chinese females, which may result from different genetic factors. We evaluated the associations of diabetes, combined with the polymorphisms in the genes of fat mass and obesity-associated gene (FTO), interleukin 6 (IL-6), and heat shock protein 60 (HSPD1), with breast cancer risk and survival in a Chinese Han population. The information on the history of diabetes was collected from 1551 incident breast cancer cases and 1605 age-frequency matched controls in Guangzhou, China. In total, 1168 cases were followed up. Diabetes was associated with both an increased risk of breast cancer [OR (95%CI): 1.67 (1.11, 2.52)] and a poor overall survival and progression free survival for breast cancer patients [HRs (95%CIs): 2.66 (1.10, 6.44) and 2.46 (1.29, 4.70), respectively]. IL-6 rs1800796 and HSPD1 rs2605039 had interactions with diabetes on breast cancer risk. Among women with CC genotype of IL-6 rs1800796 or GG genotype of HSPD1 rs2605039, diabetic individuals had a remarkably increased risk of breast cancer compared to non-diabetic women with ORs and 95%CIs of 2.53 (1.45, 4.41) and 6.40 (2.29, 17.87), respectively. GT/TT genotypes of HSPD1 rs2605039 was also associated with a better progression free survival for breast cancer patients [HR (95%CI): 0.70 (0.49, 0.99)]. Our results suggest that the contribution of diabetes to breast cancer risk might be modified by IL-6 rs1800796 and HSPD1 rs2605039. Diabetes and HSPD1 rs2605039 might also influence breast cancer prognosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178850PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462388PMC
September 2017

CATALASE2 Coordinates SA-Mediated Repression of Both Auxin Accumulation and JA Biosynthesis in Plant Defenses.

Cell Host Microbe 2017 Feb;21(2):143-155

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address:

Plants defend against pathogen attack by modulating auxin signaling and activating the salicylic acid (SA) and jasmonic acid (JA) signaling pathways. SA and JA act antagonistically in resistance to specific pathogen types, yet how plants coordinate these phytohormones remains elusive. Here we report that biotrophic-pathogen-induced SA accumulation dampens both auxin and JA synthesis by inhibiting CATALASE2 (CAT2) activity in the model plant Arabidopsis. SA suppression of CAT2 results in increased HO levels and subsequent sulfenylation of tryptophan synthetase β subunit 1, thus depleting the auxin biosynthetic precursor tryptophan. In addition, we find that CAT2 promotes JA biosynthesis by facilitating direct interaction of the JA biosynthetic enzymes ACX2 and ACX3, and thus SA repression of CAT2 inhibits JA accumulation. As such, the cat2-1 mutant exhibits increased resistance to biotrophic pathogens and increased susceptibility to necrotrophic pathogens. Our study illustrates how CAT2 coordinates SA repression of auxin accumulation and JA biosynthesis in plant defense.
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http://dx.doi.org/10.1016/j.chom.2017.01.007DOI Listing
February 2017

Nitric oxide is involved in stomatal development by modulating the expression of stomatal regulator genes in Arabidopsis.

Plant Sci 2016 Nov 10;252:282-289. Epub 2016 Aug 10.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address:

As sessile organisms, plants require many flexible strategies to adapt to the environment. Although some environmental signaling pathways regulating stomatal development have been identified, how stomatal regulators are modulated by internal and external signals to determine the final stomatal abundance requires further exploration. In our studies, we found that nitric oxide (NO) promotes stomatal development with increased stomatal index as well as the relative number of meristemoids and guard mother cells [%(M+GMC)] in NO-treated wild-type Arabidopsis plants; this role of NO was further verified in the nox1 mutant, which exhibits higher NO levels, and the noa1 mutant, which exhibits low NO accumulation. To gain insight into the molecular mechanisms underlying the effect of NO, we further assayed the expression of genes involved in stomatal development and found that NO induces the expression of the master regulators SPCH, MUTE and SCRM2 to initiate stomatal development. In addition, MPK6 is also involved in NO-promoted stomatal development, as MPK6 expression was repressed in nox1 and NO-treated plants, and transgenic plants overexpressing MPK6 were less sensitive to SNP treatment in terms of changes in the%(M+GMC). Thus, our study shows that NO promotes the production of stomata by up-regulating the expression of SPCH, MUTE and SCRM2 and down-regulating MPK6 expression.
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http://dx.doi.org/10.1016/j.plantsci.2016.08.005DOI Listing
November 2016

Allelic expression imbalance polymorphisms in susceptibility chromosome regions and the risk and survival of breast cancer.

Mol Carcinog 2017 01 29;56(1):300-311. Epub 2016 Apr 29.

Department of Statistics and Epidemiology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, The School of Public Health, Sun Yat-sen University, Guangzhou, China.

Allelic expression imbalance (AEI) has been applied to indicate potential function of genetic variants. Combining earlier results from global differential allele-specific expression analysis and genome wide association studies (GWASs), we select the single nuclear polymorphisms (SNPs) exhibiting AEI phenomenon located in breast cancer susceptibility chromosome regions, and evaluate their associations with breast cancer risk and survival. We examined the genotypes of 10 AEI SNPs in 1551 incident breast cancer cases and 1605 age-frequency matched controls from Guangzhou, China. In total, 1168 cases were followed up. MUC16 rs2591592 (AT/AA vs. TT) was associated with an increased risk of premenopausal breast cancer (OR [95%CI]: 1.30 [1.07, 1.57]); SLAMF1 rs1061217 (CT/TT vs. CC) decreased the risk of breast cancer among overweight women (OR [95%CI]: 0.74 [0.57, 0.96]) but increased the risk among normal-weight women (OR [95%CI]: 1.15 [1.01, 1.39]); ZNF331 rs8109631 (AG/AA vs. GG) and CHRAC1 rs10216653 (GC/GG vs. CC) were associated with progression free survival among breast cancer patients with negative ER/PR status and higher clinical stage (HRs [95%CIs]: 2.39 [1.14, 5.00], 1.85 [1.03, 3.32], and 0.49 [0.30, 0.80], respectively). ZNF331 rs8109631 and CHRAC1 rs10216653 were further found to represent several functional SNPs through bioinformatic analysis. In conclusion, our findings demonstrated suggestive associations of AEI polymorphisms with breast cancer risk (MUC16 rs2591592 and SLAMF1 rs1061217) and prognosis (ZNF331 rs8109631 and CHRAC1 rs10216653). © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/mc.22493DOI Listing
January 2017

A mutation of casein kinase 2 α4 subunit affects multiple developmental processes in Arabidopsis.

Plant Cell Rep 2016 May 16;35(5):1071-80. Epub 2016 Feb 16.

Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Huaihai Institute of Technology, Lianyungang, 222005, China.

Key Message: Arabidopsis CK2 α4 subunit regulates the primary root and hypocotyl elongation, lateral root formation, cotyledon expansion, rosette leaf initiation and growth, flowering, and anthocyanin biosynthesis. Casein kinase 2 (CK2) is a conserved tetrameric kinase composed of two α and two β subunits. The inhibition of CK2 activity usually results in severe developmental deficiency. Four genes (CKA1-CKA4) encode CK2 α subunit in Arabidopsis. Single mutations of CKA1, CKA2, and CKA3 do not affect the normal growth of Arabidopsis, while the cka1 cka2 cka3 triple mutants are defective in cotyledon and hypocotyl growth, lateral root development, and flowering. The inhibition of CKA4 expression in cka1 cka2 cka3 background further reduces the number of lateral roots and delays the flowering time. Here, we report the characterization of a novel knockout mutant of CKA4, which exhibits various developmental defects including reduced primary root and hypocotyl elongation, increased lateral root density, delayed cotyledon expansion, retarded rosette leaf initiation and growth, and late flowering. The examination of the cellular basis for abnormal root development of this mutant revealed reduced root meristem cells with enhanced RETINOBLASTOMA-RELATED (RBR) expression that promotes cell differentiation in root meristem. Moreover, this cka4-2 mutant accumulates higher anthocyanin in the aerial part and shows an increased expression of anthocyanin biosynthetic genes, suggesting a novel role of CK2 in modulating anthocyanin biosynthesis. In addition, the complementation test using primary root elongation assay as a sample confirms that the changed phenotypes of this cka4-2 mutant are due to the lack of CKA4. Taken together, this study reveals an essential role of CK2 α4 subunit in multiple developmental processes in Arabidopsis.
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http://dx.doi.org/10.1007/s00299-016-1939-5DOI Listing
May 2016

WD40-REPEAT 5a functions in drought stress tolerance by regulating nitric oxide accumulation in Arabidopsis.

Plant Cell Environ 2017 Apr 18;40(4):543-552. Epub 2016 Apr 18.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Nitric oxide (NO) generation by NO synthase (NOS) in guard cells plays a vital role in stomatal closure for adaptive plant response to drought stress. However, the mechanism underlying the regulation of NOS activity in plants is unclear. Here, by screening yeast deletion mutants with decreased NO accumulation and NOS-like activity when subjected to H O stress, we identified TUP1 as a novel regulator of NOS-like activity in yeast. Arabidopsis WD40-REPEAT 5a (WDR5a), a homolog of yeast TUP1, complemented H O -induced NO accumulation of a yeast mutant Δtup1, suggesting the conserved role of WDR5a in regulating NO accumulation and NOS-like activity. This note was further confirmed by using an Arabidopsis RNAi line wdr5a-1 and two T-DNA insertion mutants of WDR5a with reduced WDR5a expression, in which both H O -induced NO accumulation and stomatal closure were repressed. This was because H O -induced NOS-like activity was inhibited in the mutants compared with that of the wild type. Furthermore, these wdr5a mutants were more sensitive to drought stress as they had reduced stomatal closure and decreased expression of drought-related genes. Together, our results revealed that WDR5a functions as a novel factor to modulate NOS-like activity for changes of NO accumulation and stomatal closure in drought stress tolerance.
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http://dx.doi.org/10.1111/pce.12723DOI Listing
April 2017
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