Publications by authors named "Fei Qiu"

39 Publications

The functional role of inherited CDKN2A variants in childhood acute lymphoblastic leukemia.

Pharmacogenet Genomics 2021 Aug 6. Epub 2021 Aug 6.

Department of Hematology/Oncology Institute of Pediatrics, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, China Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas, USA Institute of Pediatrics and Department of Hematology and Oncology, Children's Hospital of Fudan University, National Children's Medical Center, the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Objective: Genetic alterations in CDKN2A tumor suppressor gene on chromosome 9p21 confer a predisposition to childhood acute lymphoblastic leukemia (ALL). Genome-wide association studies have identified missense variants in CDKN2A associated with the development of ALL. This study systematically evaluated the effects of CDKN2A coding variants on ALL risk.

Methods: We genotyped the CDKN2A coding region in 308 childhood ALL cases enrolled in CCCG-ALL-2015 clinical trials by Sanger Sequencing. Cell growth assay, cell cycle assay, MTT-based cell toxicity assay, and western blot were performed to assess the CDKN2A coding variants on ALL predisposition.

Results: We identified 10 novel exonic germline variants, including 6 missense mutations (p.A21V, p.G45A and p.V115L of p16INK4A; p.T31R, p.R90G, and p.R129L of p14ARF) and 1 nonsense mutation and 1 heterozygous termination codon mutation in exon 2 (p16INK4A p.S129X). Functional studies indicate that five novel variants resulted in reduced tumor suppressor activity of p16INK4A, and increased the susceptibility to the leukemic transformation of hematopoietic progenitor cells. Compared to other variants, p.H142R contributes higher sensitivity to CDK4/6 inhibitors.

Conclusion: These findings provide direct insight into the influence of inherited genetic variants at the CDKN2A coding region on the development of ALL and the precise clinical application of CDK4/6 inhibitors.
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http://dx.doi.org/10.1097/FPC.0000000000000451DOI Listing
August 2021

Prevalence of depression among Chinese medical students: A systematic review and meta-analysis.

Psychol Health Med 2021 Jul 7:1-17. Epub 2021 Jul 7.

Cardiovascular Department, Cardiovascular Research Institute of Traditional Chinese Medicine, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The prevalence of depression continues to increase among medical students in China, and higher than that of other majors, which is a potential risk for medical students and their patients. This study aimed to observe the prevalence of depression in Chinese medical students and also the correlation between them. All cross-sectional studies on the prevalence of depression in Chinese medical students were retrieved from PubMed, Embase, the Cochrane Database of Systematic Reviews, CNKI, and Wanfang. An 11-item checklist recommended by the Agency for Healthcare Research and Quality was adopted to evaluate the methodological quality of the included studies. Software Stata 12.0 was used to analyze the data. Registration: PROSPERO, CRD42020169681. The prevalence of depression among medical students in China was 27%. The subgroup analysis showed significant differences in the prevalence of depression in different regions. The sleep quality was a significant heterogeneous source of depression. Medical students with sleep disorders were more than three times as likely to report depression. The prevalence of depression in Chinese medical students is relatively high, and medical students with sleep disorders are more likely to have depression problems. Regular screening and appropriate intervention are recommended for these mental health problems.
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http://dx.doi.org/10.1080/13548506.2021.1950785DOI Listing
July 2021

A new algorithm for evaluating reservoir density based on X-ray logging technology.

Appl Radiat Isot 2021 Sep 4;175:109793. Epub 2021 Jun 4.

School of Geosciences, China University of Petroleum, Qingdao, 266580, China.

Rock density is an important parameter to provide critical information for evaluating both conventional and unconventional reservoirs. During the drilling process, it's a huge challenge to eliminating the negative effects of irregular mud cake formed in drilling fluid deposition to evaluating reservoir information accurately. However, the calibration of density measurement by correction charts would usually generate large errors, and the parameters that need to be corrected are often unpredictable. Therefore, based on the X-ray density logging technology, while eliminating the radioactive hazards of the isotope gamma source (Cs), a new method is proposed to address the problem through the energy spectrum information from four detectors. Theoretically, this method would analyze the role of X-rays in the dual media of formation and mud cake and then integrate the energy spectrum information from four detectors, while using Newton iterative inversion to invert the parameters about formation and mud cake. As a result, the evaluation of reservoir parameters can be achieved without correcting the mud cake. In verifying the effectiveness of this method, a simulation example shows the high accuracy of X-ray density inversion for multiple parameters. This research provides an X-ray density inversion algorithm to realize the simultaneous calculation of formation and mud cake parameters, which is of great significance for guiding hydrocarbon exploration and production.
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http://dx.doi.org/10.1016/j.apradiso.2021.109793DOI Listing
September 2021

Association Between Mutations and Glucocorticoid Resistance in Children With Acute Lymphoblastic Leukemia.

Front Pharmacol 2021 29;12:634956. Epub 2021 Mar 29.

Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center, Guangzhou, China.

Treatment outcomes in children with acute lymphoblastic leukemia (ALL) have been improved substantially, with a cure rate exceeding 80% using conventional therapy. However, the outcome for patients with relapsed/refractory ALL remains unsatisfactory, despite the fact that these patients generally receive more intense therapy. Glucocorticoid (GC) resistance is a leading cause of treatment failure and relapse in ALL. Abnormal transcription and/or translation is strongly associated with GC resistance, but the underlying molecular mechanism and the clinical value of NR3C1 alterations with GC resistance in ALL treatment remain unclear. This study applied panel sequencing to 333 newly diagnosed and 18 relapsed ALL samples to characterize the link between NR3C1 and ALL further. We identified mutations in three patients with newly diagnosed ALL (0.9%) and two patients with relapsed ALL (11.1%). Functional analyses revealed that four of these five mutations (p. R477H, p. Y478C, p. P530fs, and p. H726P) were loss-of-function (LoF) mutations. A drug sensitivity test further showed that LoF mutations influence GC resistance. Saturated mutagenesis of hotspot R477 demonstrated the importance of this residue for NR3C1 function. The dominant-negative effect of p. R477C and p. R477S and the non-dominant negative effect of p. R477H and p. Y478C suggests multiple mechanisms underlying GC resistance. Thus, primary or acquired genomic lesions in may play a critical role in GC resistance and contribute to ALL treatment failure and/or relapse.
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http://dx.doi.org/10.3389/fphar.2021.634956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039513PMC
March 2021

Nicotinate-curcumin inhibits AngII-induced vascular smooth muscle cell phenotype switching by upregulating Daxx expression.

Cell Adh Migr 2021 12;15(1):116-125

School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.

Phenotypic switching is the main cause of the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). We previously showed that Daxx exerted negative regulatory effect on AngII-induced VSMC proliferation and migration. However, the function of Daxx in VSMC phenotype switching remained unknown. Nicotinate-curcumin (NC) is an esterification derivative of niacin and curcumin that can prevent the formation of atherosclerosis. We found that NC significantly decreased AngII-induced VSMC phenotype switching. Furthermore, NC significantly inhibited AngII-induced cell proliferation and migration. Moreover, NC upregulated Daxx expression and regulated the PTEN/Akt signaling pathway. We concluded that NC inhibited AngII-induced VSMC phenotype switching by regulating the PTEN/Akt pathway, and through a mechanism that might be associated with the upregulation of Daxx expression.
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http://dx.doi.org/10.1080/19336918.2021.1909899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043179PMC
December 2021

Role of prenatal imaging in the diagnosis and management of fetal facio-cervical masses.

Sci Rep 2021 01 14;11(1):1385. Epub 2021 Jan 14.

Department of Radiology, Women's Hospital, Zhejiang University School of Medicine, Xueshi Rd No. 1, Hangzhou, Zhejiang, People's Republic of China.

Congenital facio-cervical masses can be a developmental anomaly of cystic, solid, or vascular origin, and have an inseparable relationship with adverse prognosis. This retrospective cross-sectional study aimed at determining on the prenatal diagnosis of congenital facio-cervical masses, its management and outcome in a large tertiary referral center. We collected information on prenatal clinical data, pregnancy outcomes, survival information, and final diagnosis. Out of 130 cases of facio-cervical masses, a total of 119 cases of lymphatic malformations (LMs), 2 cases of teratoma, 2 cases of thyroglossal duct cyst, 4 cases of hemangioma, 1 case of congenital epulis, and 2 cases of dermoid cyst were reviewed. The accuracy of prenatal ultrasound was 93.85% (122/130). Observations of diameters using prenatal ultrasound revealed that the bigger the initial diameter is, the bigger the relative change during pregnancy. Magnetic resonance imaging (MRI) revealed that 2 cases of masses were associated with airway compression. In conclusion, ultrasound has a high overall diagnostic accuracy of fetal face and neck deformities. Prenatal US can enhance the management of ambulatory monitoring and classification. Furthermore, MRI provided a detailed assessment of fetal congenital malformations, as well as visualization of the trachea, presenting a multi-dimensional anatomical relationship.
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http://dx.doi.org/10.1038/s41598-021-80976-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809128PMC
January 2021

4-Hydroxyphenyl Retinamide Preferentially Targets FLT3 Mutated Acute Myeloid Leukemia via ROS Induction and NF-κB Inhibition.

Curr Med Sci 2020 Oct 29;40(5):810-816. Epub 2020 Oct 29.

Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center, Guangzhou, 510623, China.

FMS-like tyrosine kinase 3 (FLT3) mutation is strongly associated with poor prognosis in acute myeloid leukemia (AML). Though many FLT3 inhibitors have been developed for clinical application with 34%-56% complete remission rate, patients would develop resistance sooner or later after initial response to tyrosine kinase inhibitors (TKIs), such as gilteritinib. And increasing studies have shown that several resistance related mutations of FLT3 emerged during the AML progression. Thus, further investigation is warranted for these FLT3 AML patients to achieve a better treatment outcome. 4-Hydroxyphenyl retinamide (4-HPR) has been investigated extensively in animal models and clinical trials as an anticancer/chemopreventive agent and is currently used for protection against cancer development/recurrence, with minimal side effects. In this study, we performed gene-set enrichment analysis and found that down-regulated genes induced by 4-HPR were associated with FLT3-ITD gene sets. CD34 AML stem/progenitor cells separated from 32 AML samples were treated with 4-HPR. Correlation analysis showed that AML cells with FLT3-ITD genetic alteration were more sensitive to 4-HPR treatment than those without FLT3-ITD. Next, we treated 22 primary AML cells with 4-HPR and found that 4-HPR was more toxic to AML cells with FLT3-ITD. These results indicated that 4-HPR was preferentially cytotoxic to all FLT3-ITD AML cells irrespective of stem/progenitor cells or blast cells. 4-HPR-induced reactive oxygen species (ROS) production and NF-κB inhibition might be the reason of 4-HPR selectivity on FLT3 mutated AML cells.
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http://dx.doi.org/10.1007/s11596-020-2259-0DOI Listing
October 2020

The Smart Dual-Stimuli Responsive Nanoparticles for Controlled Anti-Tumor Drug Release and Cancer Therapy.

Anticancer Agents Med Chem 2021 ;21(10):1202-1215

School of Medicine, Huaqiao University, Quanzhou, Fujian Province, 362021, China.

Background: In recent years, the emergence of stimuli-responsive nanoparticles has made drug delivery more efficient. As an intelligent and effective targeted delivery platform, it can reduce the side effects generated during drug transportation while enhancing the treatment efficacy. The stimuli-responsive nanoparticles can respond to different stimuli at corresponding times and locations to deliver and release their drugs and associated therapeutic effects.

Objective: This review aims to inform researchers on the latest advances in the application of dual-stimuli responsive nanoparticles in precise drug delivery, with special attention to their design, drug release properties, and therapeutic effects. Syntheses of nanoparticles with simultaneous or sequential responses to two or more stimuli (pH-redox, pH-light, redox-light, temperature-magnetic, pH-redox-temperature, redox-enzyme-light, etc.) and the applications of such responsivity properties for drugs control and release have become a hot topic of recent research.

Methods: A database of relevant information for the production of this review was sourced, screened and analyzed from Pubmed, Web of Science, SciFinder by searching for the following keywords: "dual-stimuli responsive", "controlled release", "cancer therapy", "synergistic treatment".

Results: Notably, the nanoparticles with dual-stimuli responsive function have an excellent control effect on drug delivery and release, playing a crucial part in the treatment of tumors. They can improve the encapsulation and delivery efficiency of hydrophobic chemotherapy drugs, combine chemo-photothermal therapies, apply imaging function in the diagnosis of tumors and even conduct multi-drug delivery to overcome Multi-Drug Resistance (MDR).

Conclusion: With the development of smart dual-stimuli responsive nanoparticles, cancer treatment methods have become more diverse and effective. All the stimuli-responsive nanoparticles functionalities exhibit their characteristics individually within the single nanosystem.
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http://dx.doi.org/10.2174/1871520620666200924110418DOI Listing
January 2021

Direct Interaction of Daxx and Androgen Receptor Is Required for Their Regulatory Activity in Cholesterol Biosynthesis.

Pharmacology 2021 21;106(1-2):29-36. Epub 2020 Jul 21.

Medical School, Hunan University of Chinese Medicine, Changsha, China,

Introduction: Homeostasis of cholesterol is crucial for cellular function, and dysregulated cholesterol biosynthesis is a metabolic event that can lead to hepatic and cardiovascular abnormalities.

Objective: The aim of this study was to investigate the effects and mechanisms of domain-associated protein (Daxx) and androgen receptor (AR) on intracellular cholesterol synthesis.

Methods: HepG2 cells were transfected with pCDNA3.1(+)/Daxx plasmid or treated with testosterone propionate to observe the effects of Daxx and AR on intracellular cholesterol levels. Co-immunoprecipitation experiments were performed to identify the interaction between Daxx and AR and to explore the regulatory effects of this interaction on cholesterol synthesis.

Results: Our experiments showed that AR promoted cholesterol synthesis and accumulation by activating sterol-regulatory element-binding protein isoform 2. AR-induced cholesterol synthesis was inhibited by Daxx; however, the expression of AR was not affected. Further studies demonstrated the existence of direct binding between Daxx and AR and this interaction was required to suppress AR activity.

Conclusions: The Daxx-mediated antagonism of AR depicts a more complete picture as to how Daxx regulates intracellular cholesterol level and provides a new target for treatment of atherosclerosis.
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http://dx.doi.org/10.1159/000506488DOI Listing
March 2021

A high-sensitive sensor with HEPES-enhanced electrochemiluminescence of benzo[3]uril for Fe and its application in human serum.

Analyst 2020 Mar 17;145(5):1810-1816. Epub 2020 Jan 17.

Key laboratory of macrocyclic and supramolecular chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China.

An electrochemiluminescence (ECL) sensor based on a benzo[3]uril-modified glassy carbon electrode with sensitized luminescence, with the coexistence of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) as the coreactant, was successfully constructed. The sensitization mechanism was proposed by analyzing the results of the control experiments for establishing the relationship of the luminescence effect with the concentration of HEPES. Under the optimized conditions, the fabricated sensor system was applied for the detection of Fe in an aqueous solution with good sensitivity and selectivity. A low detection limit of 0.41 nM was achieved, indicating superior sensor performance over the previous analytical methods. The ECL sensor system was employed for the detection of Fe in human serum samples to produce excellent recoveries ranging from 96.17% to 101.81%.
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http://dx.doi.org/10.1039/c9an02156fDOI Listing
March 2020

[Daxx overexpression inhibits AngⅡ-induced proliferation and migration in vascular smooth muscle cells].

Nan Fang Yi Ke Da Xue Xue Bao 2019 Oct;39(10):1173-1179

School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.

Objective: To construct a recombinant lentiviral expression vector pCDH-Daxx-EGFP to investigate the effect of Daxx on the proliferation of vascular smooth muscle cells (VSMCs).

Methods: The recombinant lentiviral expression vector pCDHDaxx-EGFP was constructed using PCR-based accurate synthesis method. After identification by sequencing and enzyme digestion, the recombinant lentiviral vector was contransfected into 293T cells with lentivirus packaging vector. The recombinant lentivirus particles were collected and purified to infect VSMCs, whose expression of Daxx was detected with Western boltting. The cells infected with the empty vector pCDH-EGFP or pCDH-Daxx-EGFP were incubated in serum-free medium or in the presence of angiotensin Ⅱ (AngⅡ). The cell viability was determined with MTT assay, and the cell cycle changes were analyzed with flow cytometry. The cell migration ability was assessed using a scratch wound healing assay. The expression of p-Akt protein in the cells was detected using Western blotting.

Results: Double enzyme digestion and sequencing confirmed successful construction of the recombinant plasmid. Compared with the cells infected with the empty vector, the cells infected with pCDH-Daxx-EGFP exhibited significantly increased expressions of Daxx protein ( < 0.05). AngⅡ treatment of the cells infected with the pCDH-Daxx-EGFP, as compared with the cells infected with the empty vector, significantly lowered the cell viability, S phase cell ratio and cell migration ability ( < 0.05), and significantly decreased the expression level of p-Akt protein ( < 0.05).

Conclusions: We successfully constructed the recombinant lentiviral vector pCDH-Daxx-EGFP and overexpressed Daxx in primary cultured VSMCs using this vector. Daxx overexpression can inhibit AngⅡ-induced proliferation and migration in VSMCs probably by regulating p-Akt protein.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2019.10.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867952PMC
October 2019

Functional genomics analysis reveals two novel genes required for littorine biosynthesis.

New Phytol 2020 03 28;225(5):1906-1914. Epub 2019 Nov 28.

Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation, SWU-TAAHC Medicinal Plant Joint R&D Centre, School of Life Sciences, Southwest University, Chongqing, 400715, China.

Some medicinal plants of the Solanaceae produce pharmaceutical tropane alkaloids (TAs), such as hyoscyamine and scopolamine. Littorine is a key biosynthetic intermediate in the hyoscyamine and scopolamine biosynthetic pathways. However, the mechanism underlying littorine formation from the precursors phenyllactate and tropine is not completely understood. Here, we report the elucidation of littorine biosynthesis through a functional genomics approach and functional identification of two novel biosynthesis genes that encode phenyllactate UDP-glycosyltransferase (UGT1) and littorine synthase (LS). UGT1 and LS are highly and specifically expressed in Atropa belladonna secondary roots. Suppression of either UGT1 or LS disrupted the biosynthesis of littorine and its TA derivatives (hyoscyamine and scopolamine). Purified His-tagged UGT1 catalysed phenyllactate glycosylation to form phenyllactylglucose. UGT1 and LS co-expression in tobacco leaves led to littorine synthesis if tropine and phenyllactate were added. This identification of UGT1 and LS provides the missing link in littorine biosynthesis. The results pave the way for producing hyoscyamine and scopolamine for medical use by metabolic engineering or synthetic biology.
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http://dx.doi.org/10.1111/nph.16317DOI Listing
March 2020

The high selective chemo-sensors for TNP based on the mono- and di-substituted multifarene[2,2] with different fluorescence quenching mechanism.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Feb 13;226:117583. Epub 2019 Oct 13.

Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang, 550025, PR China.

The chem-sensors, based on the triazole-CH-anthracene-functionalized multifarene[2,2] were successfully synthesized, which could efficiently and rapidly detect 2,4,6-trinitrophenol (TNP). The high specificities of the proposed macrocyclic sensors were achieved by selective response for TNP in the existence of other competing phenolic compounds, and the limits of detection in ∼10 mol/L range were produced to confirm the high sensitivities of the chem-sensors, which could be attributed to the mechanism of electron and resonance energy transfer processes in the complexes with the supramolecular interactions. H NMR titration analysis revealed the actual binding position should be the triazole rings of sensors with the hydroxyl group on TNP to offer a hydrogen bonding. The extraordinary sensing properties endued the compounds as sensitive fluorometric chem-sensors for the potential application of TNP detection.
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http://dx.doi.org/10.1016/j.saa.2019.117583DOI Listing
February 2020

ASF1A regulates H4 phosphorylation and promotes autophagy in colon cancer cells via a kinase activity.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):2754-2763

a Department of Gastrointestinal Surgery, Jining No. 1 People's Hospital , Jining , China.

Colon cancer is one of the most malignant cancers. Histone modification is closely related to tumour development. Our study explored the functions of anti-silencing function 1A (ASF1A) on H4 in colon cancer cells. Colon cancer cell lines and clinical specimens were obtained and/or transfected with full length ASF1A or interference mRNA to mimic or silence of ASF1A expression. Immunoprecipitation and GST pull down was used to target targeting ASF1A or H4. Cells were transfected with H4- or H4-expressing. An kinase activity assay was set to determine whether ASF1A could phosphorylate H4. The severity of autophagy was measured by detecting number of autophagosomes, number of EGFP-LC3, LC3-II/I, percentage of degradation and expression of autophagy associated gene (ATG). ASF1A positively regulated H4; Immunoprecipitation assay and GST pull down results showed that ASF1A interacted directly with H4. In addition, ASF1A silence inhibited autophagosomes number, EGFP-LC3 number, LC3-II/I, percentage of degradation and ATG expression. Moreover, H4 impaired the promoting autophagy effects of ASF1A. The ASF1A-H4 axis promoted colon cancer autophagy via transcriptional regulation of ATG genes. ASF1A regulated H4 and promotes autophagy in colon cancer cells via a kinase activity through regulation of ATG.
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http://dx.doi.org/10.1080/21691401.2019.1617725DOI Listing
December 2019

Clinical significance of serum miR-25 as a diagnostic and prognostic biomarker in human gastric cancer.

Cancer Biomark 2019 ;24(4):477-483

Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Background And Objective: MicroRNAs (miRNAs) are under investigation as novel diagnostic and prognostic biomarkers in several malignancies, including gastric cancer (GC). miR-25 was overexpressed in GC tissues, and higher miR-25 expression was statistically correlated with aggressive clinicopathological characteristics. In our study, we investigate the associations of serum miR-25 level with the clinicopathological characteristics, diagnosis and prognosis of GC patients.

Methods: Serum samples from 184 GC patients, 56 gastritis patients and 78 healthy controls were subjected to real-time quantitative polymerase chain reaction (RT-qPCR), and the relationship between micR-25 level and cliniopathological characteristics including diagnosis and prognosis was explored.

Results: Compared with the gastritis and healthy patients, serum miR-25 level was significantly up-regulated in patients with GC. Using a cut-off of 0.042, the level of miR-25 was significantly increased in serum samples from cancer patients; Using this test cancer patients were identified with 67.3-69.4% sensitivity and 80.4%-81.0% specificity. High serum miR-25 level was significantly associated with depth of invasion, lymph node metastasis and stage of disease. In univariate and multivariate analyses, miR-25 was an independent prognostic factor for overall survival (OS). Moreover, high serum miR-25 level was correlated with poor prognosis in patients subgroups stratified by tumor size, depth of invasion and lymph node metastasis. Serum miR-25 level was increased in both prominent serosal invasion group and lymph node metastasis group. Furthermore, stratified analysis showed that the TNM stage I-VI patients with high serum miR-25 level had poor prognosis than those with low serum miR-25 level.

Conclusions: Serum levels of miR-25 could improve gastric cancer screening, and as the better diagnostic and prognostic marker of gastric cancer.
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http://dx.doi.org/10.3233/CBM-182213DOI Listing
August 2019

A Phenylpyruvic Acid Reductase Is Required for Biosynthesis of Tropane Alkaloids.

Org Lett 2018 12 4;20(24):7807-7810. Epub 2018 Dec 4.

Key Laboratory of Eco-environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences , Southwest University , Chongqing 400715 , China.

Solanaceous medicinal plants produce tropane alkaloids (TAs). We discovered a novel gene from Atropa belladonna, AbPPAR, which encodes a phenylpyruvic acid reductase required for TA biosynthesis. AbPPAR was specifically expressed in root pericycles and endodermis. AbPPAR was shown to catalyze reduction of phenylpyruvic acid to phenyllactic acid, a precursor of TAs. Suppression of AbPPAR disrupted TA biosynthesis through reduction of phenyllactic acid levels. In summary, we identified a novel enzyme involved in TA biosynthesis.
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http://dx.doi.org/10.1021/acs.orglett.8b03236DOI Listing
December 2018

A Novel UDP-Glycosyltransferase of Converts Tyrosol to Specifically Produce Icariside D2.

Biomed Res Int 2018 20;2018:7970590. Epub 2018 Jun 20.

College of Pharmaceutical Sciences, Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Ministry of Education), Southwest University, Chongqing 400715, China.

is a Tibetan native herbal plant belonging to the family of Crassulaceae, which produces the pharmaceutical icariside D2 with the activities of inhibiting angiotensin-converting enzyme and killing leukemia cancer cells. In this study, we functionally characterized a novel UDP-glycosyltransferase (RcUGT1) that converted tyrosol to specifically produce icariside D2 from . at molecular and biochemical levels. was highly expressed in flowers and roots, while the icariside D2 content was much higher in stems than that in other organs, suggesting the potential translocation of icariside D2 from flowers and roots to stems. The high production of icariside D2 in stems provided a reasonable suggestion to farmers to harvest stems instead of roots for icariside D2 production. Enzymatic assays of recombinant RcUGT1 indicated that it converted tyrosol to specifically form icariside D2, with the values of m 0.97±0.10 mM, max 286±8.26 pKat/mg, cat 0.01552 s, and cat/m 159.55 s M. Functional identification of RcUGT1 facilitated the icariside D2 production through metabolic engineering in plants or synthetic biology in microbes.
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http://dx.doi.org/10.1155/2018/7970590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031081PMC
January 2019

Correlation of IGFBP-6 expression with apoptosis and migration of colorectal carcinoma cells.

Cancer Biomark 2018 ;21(4):893-898

Colorectal cancer (CRC) is one of the most common malignant tumors in digestive tract. Previous study found close correlation between insulin-like growth factor binding proteins (IGFBPs) and occurrence of multiple tumors. This study aims to analyze the effects of IGFBP6 on the apoptosis and migration of tumor cells, and to investigate underlying mechanism. HCT-116 or SW480 cell was cultured with 1.0 mg/l, 10 mg/l and 100 mg/l IGFBP-6. MTT assay was employed to test the proliferation activity of tumor cells after differential treatment. The cell cycle of tumor cells was detected by flow cytometry, while Transwell assay was used to quantify the invasion and migration of tumor cells after IGFBP-6 intervention. In experimental group with IGFPB-6 application, the proliferation rate of HCG-116 or SW480 cells was gradually decreased with higher concentrations of IGFBP-6 (p< 0.05). The ratio of cells at G0/G1 phase was increased while S phase and G2/M phase ratio were all decreased with IGFPB-6. With further elevated concentration of IGFPB-6, there was more potency of higher G0/G1 ratio and lower S phase or G2/M phase (p< 0.05). Both invasion and migration ability of HCT-116 or SW480 cells in experimental group were decreased. With elevated IGFBP-6 concentration, cell invasion and migration were further weakened (p< 0.05).IGFBP-6 could inhibit invasion and migration of colorectal carcinoma cells possibly via inhibiting proliferation activity and arresting cell cycle of HCT-116 or SW480 cells.
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http://dx.doi.org/10.3233/CBM-170947DOI Listing
August 2018

Cell surface expression of nucleolin mediates the antiangiogenic and antitumor activities of kallistatin.

Oncotarget 2018 Jan 16;9(2):2220-2235. Epub 2017 Dec 16.

Institute of Molecular Medicine, Huaqiao University, Quanzhou, China.

Kallistatin is a unique serine proteinase inhibitor and heparin-binding protein. A previous study conducted by our group indicated that kallistatin has antiangiogenic and antitumoral activities. In the present study, we report that kallistatin specifically binds to membrane surface-expressed nucleolin with high affinity. Antibody-mediated neutralization or siRNA-induced nucleolin knockdown results in loss of kallistatin suppression of endothelial cell proliferation and migration and tumor angiogenesis and growth . In addition, we show that kallistatin is internalized and transported into cell nuclei of endothelial cells via nucleolin. Within the nucleus, kallistatin inhibits the phosphorylation of nucleolin, which is a critical step required for cell proliferation. Thus, we demonstrate that nucleolin is a novel functional receptor of kallistatin that mediates its antiangiogenic and antitumor activities. These findings provide mechanistic insights into the inhibitory effects of kallistatin on endothelial cell growth, tumor cell proliferation, and tumor-related angiogenesis.
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http://dx.doi.org/10.18632/oncotarget.23346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788634PMC
January 2018

Enhancing Tropane Alkaloid Production Based on the Functional Identification of Tropine-Forming Reductase in , a Tibetan Medicinal Plant.

Front Plant Sci 2017 16;8:1745. Epub 2017 Oct 16.

Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), Chongqing Key Laboratory of Plant Ecology and Resources Research in Three Gorges Reservoir Region, SWU-TAAHC Medicinal Plant Joint R&D Centre, School of Life Sciences, Southwest University, Chongqing, China.

, a native herbal plant species in Tibet, is one of the most effective producers of tropane alkaloids. However, the tropane alkaloid biosynthesis in this plant species of interest has yet to be studied at the molecular, biochemical, and biotechnological level. Here, we report on the isolation and characterization of a putative short chain dehydrogenase (SDR) gene. Sequence analysis showed that SlTRI belonged to the SDR family. Phylogenetic analysis revealed that SlTRI was clustered with the tropine-forming reductases. and the other TA-biosynthesis genes, including () and β (), were preferably or exclusively expressed in the . roots. The tissue profile of suggested that this gene might be involved in tropane alkaloid biosynthesis. By using GC-MS, SlTRI was shown to catalyze the tropinone reduction to yield tropine, the key intermediate of tropane alkaloids. With the purified recombinant SlTRI from , an enzymatic assay was carried out; its result indicated that SlTRI was a tropine-forming reductase. Finally, the role of SlTRI in promoting the tropane alkaloid biosynthesis was confirmed through metabolic engineering in . . Specifically, hairy root cultures of . were established to investigate the effects of SlTRI overexpression on tropane alkaloid accumulation. In the -overexpressing root cultures, the hyoscyamine contents were 1.7- to 2.9-fold higher than those in control while their corresponding scopolamine contents were likewise elevated. In summary, this functional identification of has provided for a better understanding of tropane alkaloid biosynthesis. It also provides a candidate gene for enhancing tropane alkaloid biosynthesis in . via metabolic engineering.
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http://dx.doi.org/10.3389/fpls.2017.01745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650612PMC
October 2017

A method to describe inelastic gamma field distribution in neutron gamma density logging.

Appl Radiat Isot 2017 Nov 21;129:189-195. Epub 2017 Aug 21.

School of Geosciences, China University of Petroleum, Qingdao 266580, China.

Pulsed neutron gamma density logging (NGD) is of great significance for radioprotection and density measurement in LWD, however, the current methods have difficulty in quantitative calculation and single factor analysis for the inelastic gamma field distribution. In order to clarify the NGD mechanism, a new method is developed to describe the inelastic gamma field distribution. Based on the fast-neutron scattering and gamma attenuation, the inelastic gamma field distribution is characterized by the inelastic scattering cross section, fast-neutron scattering free path, formation density and other parameters. And the contribution of formation parameters on the field distribution is quantitatively analyzed. The results shows the contribution of density attenuation is opposite to that of inelastic scattering cross section and fast-neutron scattering free path. And as the detector-spacing increases, the density attenuation gradually plays a dominant role in the gamma field distribution, which means large detector-spacing is more favorable for the density measurement. Besides, the relationship of density sensitivity and detector spacing was studied according to this gamma field distribution, therefore, the spacing of near and far gamma ray detector is determined. The research provides theoretical guidance for the tool parameter design and density determination of pulsed neutron gamma density logging technique.
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http://dx.doi.org/10.1016/j.apradiso.2017.08.024DOI Listing
November 2017

Kallistatin protects against bleomycin-induced idiopathic pulmonary fibrosis by inhibiting angiogenesis and inflammation.

Am J Transl Res 2017 15;9(3):999-1011. Epub 2017 Mar 15.

Institute of Molecular Medicine, Huaqiao University Quanzhou 362021, China.

Aberrant angiogenesis and vascular remodeling are the main features of idiopathic pulmonary fibrosis. Kallistatin is an anti-angiogenic peptide with known effects on endothelial cells. This study aimed to demonstrate that kallistatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in a rat model by inhibiting angiogenesis. Twenty-five rats were randomly divided into five experimental groups: (A) Saline only (SA)-as the negative control, (B) BLM only (BLM)-as the model group, (C) BLM and 0.1 mg/kg kallistatin (L-Kal), (D) BLM and 0.5 mg/kg kallistatin (M-Kal), and (E) BLM and 2.5 mg/kg kallistatin (H-Kal). Fibrillar collagen was quantified by Masson's trichrome and hematoxylin-eosin staining. Transforming growth factor-β1 (TGF-β1), α-smooth-muscle-actin (α-SMA) and microvascular density (MVD) were measured by immunohistochemistry. Vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), and tumor necrosis factor-α (TNF-α) were assayed by Western immunoblotting or ELISA. Daily administration of kallistatin attenuated fibrosis in BLM-induced pulmonary fibrosis, as shown by histology. During inflammation from BLM-induced pulmonary fibrosis, kallistatin reduced the number of inflammatory cells infiltrating the bronchoalveolar lavage fluid. Kallistatin also inhibited VEGF expression and phosphorylation of VEGFR2 (Flk-1). In vitro, kallistatin blocked tube formation by inhibiting Flk-1 and GSK-3β phosphorylation. The results demonstrated that continuous administration of kallistatin attenuated BLM-induced pulmonary fibrosis and improved survival of BLM rats. Reducing pulmonary fibrosis was achieved by partial inhibition of pulmonary inflammation and angiogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5375993PMC
March 2017

Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma.

Oncol Rep 2017 Apr 10;37(4):2071-2078. Epub 2017 Mar 10.

The First Intensive Care Unit, The First People's Hospital of Jining, Jining, Shandong 272100, P.R. China.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. More than 80% of patients with HCC are not good candidates for curative surgical resection due to advanced liver cirrhosis caused by underlying chronic hepatitis virus (B or C) infection. Sorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced HCC. Although, sorafenib currently sets the new standard for advanced HCC treatment, tumor response rates are usually quite low. An understanding of the underlying mechanisms for sorafenib resistance is critical. In the present study, we found that adenine nucleotide translocator 2 (ANT2) was upregulated in sorafenib‑resistant HCC Huh7 cells (Huh7-R) and its overexpression promoted sorafenib resistance. ANT2 induced the formation of cancer-initiating cell (CIC) phenotypes and promoted metastasis-associated traits in the Huh7 cells. Silencing of miR-137 upregulated ANT2 protein expression in the Huh7 cells. miR-137 was downregulated in the Huh7-R cells, compared with that in the Huh7 cells and its restoration reversed sorafenib resistance in the Huh7-R cells. Restoration of miR-137 inhibited formation of CIC traits and attenuated the abilities of migration and invasion in the Huh7-R cells. Moreover, we demonstrated that high-intensity focused ultrasound (HIFU) in unresectable HCC upregulated serum miR-137. Combining HIFU and sorafenib may be a wise option for advanced and unresectable HCC.
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http://dx.doi.org/10.3892/or.2017.5498DOI Listing
April 2017

[Cloning and characterization of an aromatic amino acid aminotransferase(ArAT) gene involved in tropane alkaloid biosynthesis from Hyoscyamus niger].

Yao Xue Xue Bao 2017 Jan;52(1):172-9

Tropane alkaloids are anticholinergic drugs widely used clinically. Biosynthesis of tropane alkaloids in planta involves a step of transamination of phenylalanine. Based on the sequenced transcriptomes of lateral roots and leaves of Hyoscyamus niger, we found three annotated aromatic amino acid aminotransferases, which were respectively named HnArAT1, HnArAT2 and HnArAT3. Sequence analysis showed that HnArAT3 had highest similarity with the reported Atropa belladonna Ab Ar AT4, which was involved in tropane alkaloid(TA) to provide the precursor of the phenyllactic acid moiety. Tissue expression pattern analysis indicated that HnArAT3 was specifically expressed in lateral roots, where is the organ synthesizing tropane alkaloids. Then, method of virus induced gene silencing (VIGS) was used to characterize the function of HnArAT3 in H. niger. Gene expression analysis given by real-time quantitative PCR showed that all the transgenic lines had lower expression levels of HnArAT3 than the non-transgenic control, and HPLC analysis of alkaloids demonstrated significant decrease in the contents of hyoscyamine, anisodamine and scopolamine in planta. These results suggested that HnArAT3 was involved in the phenyllactic acid branch of TA biosynthetic pathway. Molecular cloning and functional identification of HnArAT3 laid the foundation for further understanding of TA biosynthesis and metabolic regulation, and also provided a new candidate gene for engineering biosynthetic pathway of tropane alkaloids.
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January 2017

Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells.

Biochem Biophys Res Commun 2016 Nov 23;480(1):139-145. Epub 2016 Sep 23.

Medical School, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China. Electronic address:

Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626-740 clearly reduced intracellular cholesterol levels and inhibited the expression of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626-740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR-mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells.
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http://dx.doi.org/10.1016/j.bbrc.2016.09.102DOI Listing
November 2016

Molecular cloning and characterization of the promoter of aldehyde dehydrogenase gene from Artemisia annua.

Biotechnol Appl Biochem 2017 Nov 7;64(6):902-910. Epub 2017 Sep 7.

Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), SWU-TAAHC Medicinal Plant Joint R&D Centre, School of Life Sciences, Southwest University, Chongqing 400715, People's Republic of China.

In recent years, although several related genes had been cloned and characterized, the role of aldehyde dehydrogenase 1 (ALDH1), the newly cloned gene involved in artemisinin biosynthesis pathway, is still not clear. In this study, a 2,100-bp ALDH1 promoter region fused with GUS reporter gene was stably transferred into Arabidopsis thaliana. Histochemical staining showed the methyl jasmonate (MeJA) and wounding treatment induced the GUS gene expression specifically in the trichomes of transgenic A. thaliana, consistent with the results that the expression level of ALDH1 gene was increased in the A. annua under MeJA and wounding treatments. Two RAA motifs (AP2/ERF binding site) but no W box (WRKY binding site) motif were identified in the ALDH1 promoter by the analysis through PLACE and plantCARE. Through the dual luciferase reporter assay, we revealed that both AaORA and AaERF2, rather than AaWRKY1, could activate the expression of ALDH1 promoter. Our study shed light on the in-depth understanding of the role of ALDH1 in artemisinin biosynthesis.
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http://dx.doi.org/10.1002/bab.1520DOI Listing
November 2017

[Cloning and functional characterization of a cDNA encoding isopentenyl diphosphate isomerase involved in taxol biosynthesis in Taxus media].

Yao Xue Xue Bao 2015 May;50(5):621-6

Taxol is one of the most potent anti-cancer agents, which is extracted from the plants of Taxus species. Isopentenyl diphosphate isomerase (IPI) catalyzes the reversible transformation between IPP and DMAPP, both of which are the general 5-carbon precursors for taxol biosynthesis. In the present study, a new gene encoding IPI was cloned from Taxus media (namely TmIPI with the GenBank Accession Number KP970677) for the first time. The full-length cDNA of TmIPI was 1 232 bps encoding a polypeptide with 233 amino acids, in which the conserved domain Nudix was found. Bioinformatic analysis indicated that the sequence of TmIPI was highly similar to those of other plant IPI proteins, and the phylogenetic analysis showed that there were two clades of plant IPI proteins, including IPIs of angiosperm plants and IPIs of gymnosperm plants. TmIPI belonged to the clade of gymnosperm plant IPIs, and this was consistent with the fact that Taxus media is a plant species of gymnosperm. Southern blotting analysis demonstrated that there was a gene family of IPI in Taxus media. Finally, functional verification was applied to identify the function of TmIPI. The results showed that biosynthesis of β-carotenoid was enhanced by overexpressing TmIPI in the engineered E. coli strain, and this suggested that TmIPI might be a key gene involved in isoprenoid/terpenoid biosynthesis.
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May 2015

[The effect of Connexin43 downregulation on biological functions of HUVEC].

Yao Xue Xue Bao 2015 Mar;50(3):298-304

Connexin43 has been shown to play a pivotal role in wound healing process. Wound repair is enhanced by acute downregulation of connexin43, by increasing proliferation and migration of keratinocyte and fibroblast. Angiogenesis is also a central feature of wound repair, but little is known about the effects of connexin43 modulation on functions of endothelial cells. We used connexin43 specific small interference RNA (siRNA) to reduce the expression of connexin43 in human umbilical vein endothelial cell (HUVEC), and investigated the effects of connexin43 downregulation on intercellular communication, viability, proliferation, migration and angiogenic activity of HUVEC. Treatment of siRNA markedly reduced the expression of connexin43 by -80% in HUVEC (P < 0.05), and decreased the intercellular communication by -65% (P < 0.05). The viability, proliferation, migration and angiogenic activity of HUVEC decreased significantly (P < 0.05), compared with that of the normal cells. The results suggest that temporally downregulation of connexin43 expression at early stage of wound to inhibit the abnormal angiogenesis characterized with leaky and inflamed blood vessels, maybe a prerequisite for coordinated normal healing process.
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March 2015

A prenyltransferase gene confirmed to be a carotenogenic CRTE gene from sweetpotato.

J Genet Genomics 2014 Nov 9;41(11):613-6. Epub 2014 Jun 9.

Agricultural and Animal Husbandry College, Tibet University, Nyingchi of Tibet 860000, China.

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http://dx.doi.org/10.1016/j.jgg.2014.04.007DOI Listing
November 2014

Breast cancer association studies in a Han Chinese population using 10 European-ancestry-associated breast cancer susceptibility SNPs.

Asian Pac J Cancer Prev 2014 ;15(1):85-91

School of Biotechnology, Southern Medical University, Guangzhou, China E-mail :

Background: Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations.

Methods: Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status.

Results: Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status.

Conclusion: In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese.
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http://dx.doi.org/10.7314/apjcp.2014.15.1.85DOI Listing
November 2014
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