Publications by authors named "Zhi Nie"

20 Publications

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PirB functions as an intrinsic suppressor in hippocampal neural stem cells.

Aging (Albany NY) 2021 06 13;13(12):16062-16071. Epub 2021 Jun 13.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.

Neural stem cells play pivotal roles during prenatal development and throughout life. Here, we report that Paired immunoglobulin-like receptor B (PirB) functions as a suppressor during brain neurogenesis in the adult mouse. PirB expression increased with age during development, and its deficiency promoted neural stem cell proliferation and differentiation and . Furthermore, we detected an increase in Type 1 neural stem cells in PirB-deficient mice compared to their wild-type littermates. PirB deficiency promoted stemness marker gene expression of Sox2 and KLF4 by activating Akt1 phosphorylation. These findings suggest that PirB inhibits the self-renewal and differentiation capacities of neural stem cells. Thus, PirB may have the potential to serve as a therapeutic target for treatment of reduced neurogenesis in adults due to aging or other pathological conditions.
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http://dx.doi.org/10.18632/aging.203134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266311PMC
June 2021

Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression.

Front Cell Dev Biol 2021 11;9:678209. Epub 2021 May 11.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China.

Glioblastoma (GBM) is the most common and malignant primary brain tumor. Glioblastoma stem cells (GSCs) not only initiate and sustain uncontrolled cell proliferation but also resistant to conventional clinical therapies including temozolomide (TMZ) dependent chemotherapy and radiotherapy, implying that there is an urgent need to identify new therapeutic strategies especially specific targeting GSCs. Here, we provide evidence showing that ivacaftor commonly applied in cystic fibrosis therapy acts as a potent inhibitor for GSCs maintenance. We found that ivacaftor promotes cellular apoptosis and represses patient-derived xenograft (PDX) tumor growth . In addition, we demonstrate that ivacaftor decreases stemness marker gene expressions of GSCs, including CD133, CD44, and Sox2. In summary, our findings reveal that ivacaftor inhibits glioblastoma progression via specifically eliminating GSCs, which opens a new avenue for GBM clinical therapy in the future.
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http://dx.doi.org/10.3389/fcell.2021.678209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147559PMC
May 2021

Decoupling-based adaptive sliding-mode synchro-position control for a dual-cylinder driven hydraulic support with different pipelines.

ISA Trans 2021 May 18. Epub 2021 May 18.

School of Information and Control Engineering, China University of Mining and Technology, Xuzhou 221116, China. Electronic address:

Dual-cylinder driving columns of a hydraulic support are required to be synchronous, with the purpose of guaranteeing the support balance and providing the roof an enough force. In addition, pipelines connecting cylinders with electro-hydraulic servo-valve have a significance influence on synchronization. Taking the length of pipelines into account, the mathematical model of a dual-cylinder driven hydraulic support is built, and the displacement-force coupling characteristic caused by the shared pump is tackled by a decoupling compensator. Following that, an adaptive sliding-mode synchro-position control strategy (ASSC) is designed based on an improved sliding mode reaching law and an adaptive law is developed to restrain the uncertainties resulted from the sub-system after decoupling. The experimental results obtained from the joint simulation platform and practical system show that the proposed controller can effectively reduce the synchronization error between two column positions and has better control performance than the PI and fuzzy PID controllers.
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http://dx.doi.org/10.1016/j.isatra.2021.05.013DOI Listing
May 2021

SH3BGRL3, transcribed by STAT3, facilitates glioblastoma tumorigenesis by activating STAT3 signaling.

Biochem Biophys Res Commun 2021 06 8;556:114-120. Epub 2021 Apr 8.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. Electronic address:

Glioblastoma (GBM) is the most aggressive tumors of the central nervous system. Here, we report that SH3 binding glutamic acid-rich protein like 3 (SH3BGRL3) was extremely highly expressed in GBM and glioma stem cells. SH3BGRL3 high expression associates with worse survival of GBM patients. Functionally, Targeting SH3BGRL3 obviously impairs GSCs self-renewal in vitro. Most importantly, we first report that SH3BGRL3 is a direct transcriptional target gene of signal transducer and activator of transcription 3 (STAT3) and thereby activating STAT3 signaling in turn. Additionally, forced expression of the constitutively activated STAT3 (STAT3-C) rescued GSCs self-renewal inhibited by SH3BGRL3 silencing. Collectively, we first identified a critical positive feedback loop between SH3BGRL3 and STAT3, which facilitates the tumorigenic potential of GBM.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.165DOI Listing
June 2021

The role of m6A modification in the biological functions and diseases.

Signal Transduct Target Ther 2021 Feb 21;6(1):74. Epub 2021 Feb 21.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, 650223, Kunming, Yunnan, China.

N-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as "readers". Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.
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http://dx.doi.org/10.1038/s41392-020-00450-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897327PMC
February 2021

SH3BGRL2 functions as a crucial tumor suppressor in glioblastoma tumorigenesis.

Biochem Biophys Res Commun 2021 Apr 19;547:148-154. Epub 2021 Feb 19.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. Electronic address:

Glioblastoma is the most common and severe primary intrinsic tumor of the central nervous system. Glioblastoma harbors glioma stem cells (GSCs) as it not only possesses self-renewal and differentiation properties but also accounts for significant chemotherapy resistance and recurrence. Thus, targeting GSCs may be essential in overcoming the resistance and recurrence thereby improving GBM treatment. However, the underlying mechanism to sustain GSCs remains largely unknown. Here, we report that SH3 domain binding glutamate-rich protein like 2 (SH3BGRL2) is weakly expressed in glioblastoma multiforme (GBM) and isocitrate dehydrogenase1 (IDH1) wildtype GBM and correlated with glioma patients' poor prognosis. Moreover, ectopic expression of SH3BGRL2 significantly inhibited GBM cell growth, migration, and GSCs self-renewal in vitro as well as tumor growth in vivo. Additionally, we found that SH3BGRL2 suppressed SOX2 and CD133 expression, which are key regulators involved in GSCs self-renewal. Collectively, our findings shed additional light on SH3BGRL2 has potential to serve as a biomarker and a potent therapeutic target for patients with glioma.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.035DOI Listing
April 2021

SH3GL3 acts as a novel tumor suppressor in glioblastoma tumorigenesis by inhibiting STAT3 signaling.

Biochem Biophys Res Commun 2021 Mar 29;544:73-80. Epub 2021 Jan 29.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. Electronic address:

Glioblastoma (GBM) is the most severe malignant tumors of the central nervous system. Glioblastoma stem cells (GSCs) are considered to account for tumor initiation, therapeutic resistance, and tumor relapse. Yet the underlying mechanisms of GSC stemness maintenance remain largely unknown. Abnormal activation of STAT3 signaling is required for GBM tumorigenesis and GSC self-renewal. In this study, we provide evidence that SH3GL3 was weakly expressed in GBM and its high expression correlated with a favorable prognosis for GBM patients. Ectopic of SH3GL3 expression considerably inhibits GBM cell malignant behaviors, including GBM cell proliferation, migration as well as GSCs self-renewal ability. Mechanistically, we first found that SH3GL3 interacts with STAT3, which thereby inhibiting STAT3 nuclear localization. Overexpression of constitutively activated (STAT3-C) restored the growth, migration and self-renewal ability impaired by overexpression of SH3GL3. Together, our work shed insight on a critical regulatory mechanism mediated by SH3GL3 to decrease the stem cell-like property and tumorigenic potential.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.040DOI Listing
March 2021

Knowledge and current practices of ICU nurses regarding aerosol therapy for patients treated with invasive mechanical ventilation: a nationwide cross-sectional study.

J Clin Nurs 2021 Jan 13. Epub 2021 Jan 13.

Department of Medical Records, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.

Background: Aerosol therapy is a routine operation for intensive care unit (ICU) nurses; however, evidence of the knowledge and current practices of ICU nurses regarding aerosol therapy for patients with invasive mechanical ventilation is insufficient in China.

Objective: This study aimed to determine the knowledge and current practices of ICU nurses regarding aerosol therapy for patients with invasive mechanical ventilation in China.

Setting: A total of 433 hospitals in 92 cities (including 31 capital cities) in 31 provinces in China participated in the study.

Methods: A questionnaire was used to investigate the knowledge and current practices of ICU nurses regarding aerosol therapy for patients treated with invasive mechanical ventilation, including 42 questions covering five aspects: sociodemographic information, aerosolization devices, atomised drugs, atomisation operation, and atomisation-related knowledge. Descriptive analyses of the distribution of the sample are reported as percentages and medians. Univariate and multivariate analysis was used to detect the factors of the interviewee's atomisation knowledge and practices scores. A STROBE checklist was used to guide the reporting of the research.

Results: Of the 1,995 questionnaires that were returned, 1,978 were analysed. Bronchodilators and glucocorticoids were the most frequently administered drugs. Seventy-four percent of the total respondents reported placing a filter on the expiratory limb during aerosol therapy, and 47% of these reported that the filter was changed once a day. Only 13% of the respondents reported always turning the heating humidifier off during aerosol therapy, and 48% never did. Knowledge about the optimal droplet size or atomisation yield was poor. Work experience in the ICU and frequency of atomisation training were the independent influencing factors for atomisation knowledge and practice scores (F=279.653, P<0.001; F=120.556, P<0.001, respectively).

Conclusions: The knowledge of ICU nurses about the optimal implementation of aerosol therapy is poor, and the current scientific knowledge about optimal implementation seemed to be applied infrequently. Atomisation-related training should be strengthened, especially for nurses with junior titles and with less work experience.

Relevance To Clinical Practice: Improving the level of ICU nurses' atomization practice ability is helpful to ensure patient safety. In clinical work, atomization expert consensus can be used to carry out relevant training and standardize atomization operation.
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http://dx.doi.org/10.1111/jocn.15639DOI Listing
January 2021

Pyrrolo [3,4-]-quinolin-9-amine compound FZU-0038-056 suppresses triple-negative breast cancer partially through inhibiting the expression of Bcl-2.

Aging (Albany NY) 2020 05 23;12(10):9621-9632. Epub 2020 May 23.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes of breast cancer; however, it lacks effective targeted therapies clinically. In this study, we found FZU-0038-056, a novel compound derived from last-stage functionalization of tetrahydro-β-carboline scaffold, showed the most potent anti-cancer activity against TNBC cells among the 42 synthesized derivatives. We found FZU-0038-056 significantly induces apoptosis in HCC1806 and HCC1937 TNBC cells. FZU-0038-056 reduces the expression levels of several anti-apoptosis proteins, including Bcl-2, Mcl-1 and XIAP. Furthermore, we found FZU-0038-056 induces apoptosis partially through inhibiting the expression of Bcl-2. Finally, we found FZU-0038-056 significantly suppresses HCC1806 xenograft tumor growth in nude mice without affecting their body weight. Therefore, FZU-0038-056 has the potential to be a new anticancer agent for treating human TNBC.
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http://dx.doi.org/10.18632/aging.103232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288966PMC
May 2020

The cumulative venous thromboembolism incidence and risk factors in intensive care patients receiving the guideline-recommended thromboprophylaxis.

Medicine (Baltimore) 2019 Jun;98(23):e15833

Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University.

Few prospective studies have reported the cumulative incidence of venous thromboembolism (VTE) in the intensive care unit (ICU), especially for patients receiving guideline-recommended VTE prophylaxis. We aimed to design a prospective observational study to investigate the cumulative incidence and risk factors of ICU-acquired VTE for those populations.We prospectively studied 281 consecutively included patients in the ICU at a single center. All patients provided informed consent. Patients received ultrasound evaluation and were followed for VTE before ICU discharge or within 28 days of ICU stay. The type of VTE thromboprophylaxis was also recorded for all patients. Variables from univariate analyses that were associated with VTE were included in the binary logistic regression analysis to determine VTE predictors. The cumulative VTE incidence with 95% confidence interval (CI) was estimated using Kaplan-Meier methods.Patients had a median age of 60 years (range, 18-89) and an acute physiology and chronic health evaluation II score of 17 (range, 4-36). Despite all patients receiving guideline-recommended thromboprophylaxis, the cumulative incidence of VTE at 7, 14, 21, and 28 days was 4.45% (95% CI 2.55-7.71), 7.14% (95% CI 4.61-10.97), 7.53% (95% CI 4.92-11.43), and 9.55% (95% CI 6.55-13.81), respectively. Central venous catheter use (P = .002, odds ratio [OR] = 4.50), Caprini score (P = .012, OR = 1.20), and ICU length of stay (P = .006, OR = 1.08) were independent risk factors related to the incidence of VTE for patients admitted to the ICU.Our prospective observational study found that the 28-day cumulative incidence of VTE was relatively high for patients admitted to the ICU, despite the use of guideline-recommended thromboprophylaxis. Patients with femoral central venous catheter, prolonged ICU length of stay, or a high Caprini score may have an increased risk of developing VTE.
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http://dx.doi.org/10.1097/MD.0000000000015833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571428PMC
June 2019

Metabolite profiling and genome-wide association studies reveal response mechanisms of phosphorus deficiency in maize seedling.

Plant J 2019 03 22;97(5):947-969. Epub 2019 Jan 22.

Maize Research Institute, Sichuan Agricultural University, 611130, Sichuan, Chengdu, China.

Inorganic phosphorus (Pi) is an essential element in numerous metabolic reactions and signaling pathways, but the molecular details of these pathways remain largely unknown. In this study, metabolite profiles of maize (Zea mays L.) leaves and roots were compared between six low-Pi-sensitive lines and six low-Pi-tolerant lines under Pi-sufficient and Pi-deficient conditions to identify pathways and genes associated with the low-Pi stress response. Results showed that under Pi deprivation the concentrations of nucleic acids, organic acids and sugars were increased, but that the concentrations of phosphorylated metabolites, certain amino acids, lipid metabolites and nitrogenous compounds were decreased. The levels of secondary metabolites involved in plant immune reactions, including benzoxazinoids and flavonoids, were significantly different in plants grown under Pi-deficient conditions. Among them, the 11 most stable metabolites showed significant differences under low- and normal-Pi conditions based on the coefficient of variation (CV). Isoleucine and alanine were the most stable metabolites for the identification of Pi-sensitive and Pi-resistant maize inbred lines. With the significant correlation between morphological traits and metabolites, five low-Pi-responding consensus genes associated with morphological traits and simultaneously involved in metabolic pathways were mined by combining metabolites profiles and genome-wide association study (GWAS). The consensus genes induced by Pi deficiency in maize seedlings were also validated by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, these genes were further validated in a recombinant inbred line (RIL) population, in which the glucose-6-phosphate-1-epimerase encoding gene mediated yield and correlated traits to phosphorus availability. Together, our results provide a framework for understanding the metabolic processes underlying Pi-deficient responses and give multiple insights into improving the efficiency of Pi use in maize.
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http://dx.doi.org/10.1111/tpj.14160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850195PMC
March 2019

Predictive modeling of treatment resistant depression using data from STAR*D and an independent clinical study.

PLoS One 2018 7;13(6):e0197268. Epub 2018 Jun 7.

Neuroscience Therapeutic Area, Janssen Research & Development, LLC, Pennington, NJ, United States of America.

Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset. We also included data from a small yet completely independent cohort RIS-INT-93 as an external test dataset. We used features from enrollment and level 1 treatment (up to week 2 response only) of STAR*D to explore the feature space comprehensively and applied machine learning methods to model TRD outcome at level 2. For TRD defined using QIDS-C16 remission criteria, multiple machine learning models were internally cross-validated in the STAR*D training dataset and externally validated in both the STAR*D testing dataset and RIS-INT-93 independent dataset with an area under the receiver operating characteristic curve (AUC) of 0.70-0.78 and 0.72-0.77, respectively. The upper bound for the AUC achievable with the full set of features could be as high as 0.78 in the STAR*D testing dataset. Model developed using top 30 features identified using feature selection technique (k-means clustering followed by χ2 test) achieved an AUC of 0.77 in the STAR*D testing dataset. In addition, the model developed using overlapping features between STAR*D and RIS-INT-93, achieved an AUC of > 0.70 in both the STAR*D testing and RIS-INT-93 datasets. Among all the features explored in STAR*D and RIS-INT-93 datasets, the most important feature was early or initial treatment response or symptom severity at week 2. These results indicate that prediction of TRD prior to undergoing a second round of antidepressant treatment could be feasible even in the absence of biomarker data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197268PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991746PMC
November 2018

Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression.

Theranostics 2016 13;6(4):533-44. Epub 2016 Feb 13.

1. Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming, 650223, China;

Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancers without effective targeted therapies. Mifepristone (MIF), a drug regularly used for abortion, has been reported to have anti-tumor activity in multiple hormone-dependent cancers, including luminal type breast cancers. In this study, we showed that MIF suppressed tumor growth of the TNBC cell lines and patient-derived xenografts in NOD-SCID mice. Furthermore, MIF reduced the TNBC cancer stem cell (CSC) population through down-regulating KLF5 expression, a stem cell transcription factor over-expressed in basal type TNBC and promoting cell proliferation, survival and stemness. Interestingly, MIF suppresses the expression of KLF5 through inducing the expression of miR-153. Consistently, miR-153 decreases CSC and miR-153 inhibitor rescued MIF-induced down-regulation of the KLF5 protein level and CSC ratio. Taken together, our findings suggest that MIF inhibits basal TNBC via the miR-153/KLF5 axis and MIF may be used for the treatment of TNBC.
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http://dx.doi.org/10.7150/thno.14315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775863PMC
December 2016

Transforming growth factor-beta increases breast cancer stem cell population partially through upregulating PMEPA1 expression.

Acta Biochim Biophys Sin (Shanghai) 2016 Feb 11;48(2):194-201. Epub 2016 Jan 11.

Pharmaceutical College of Kunming Medical University, Kunming 650500, China

The prostate transmembrane protein, androgen-induced 1 (PMEPA1) has been previously shown to promote solid malignancies in a variety of cancers, but the role and mechanisms of PMEPA1 in breast cancer has not been fully addressed. Here, we found that PMEPA1 was upregulated in breast cancer cell lines as well as in a set of clinical invasive breast ductal carcinomas. Interestingly, depletion of PMEPA1 decreased breast cancer stem cell (CSC)-enriched populations, while ectopic overexpression of PMEPA1 increased breast CSC-enriched populations. Furthermore, transforming growth factor-β (TGF-β) treatment was also found to upregulate PMEPA1 expression and the CSC-enriched populations in triple-negative breast cancer cell lines. TGF-β-induced PMEPA1 expression partially contributed to TGF-β-induced breast CSC maintenance. These findings suggest that TGF-β-PMEPA1 axis might provide new diagnosis and therapeutic targets for breast cancer treatment.
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http://dx.doi.org/10.1093/abbs/gmv130DOI Listing
February 2016

Genome-wide identification of microRNAs responding to early stages of phosphate deficiency in maize.

Physiol Plant 2016 Jun 29;157(2):161-74. Epub 2016 Jan 29.

Key laboratory of Biology and Genetic Improvement of Maize in Southwest Region, Maize Research Institute, Sichuan Agricultural University, Chengdu, 611130, China.

Phosphorus (P) is an essential element involved in numerous biochemical reactions. In plants, stress responses, such as the expression of microRNAs (miRNAs), are induced to help them adapt to low phosphate (Pi) concentrations. In this study, deep sequencing was performed using the roots and leaves of maize seedlings grown under low Pi concentrations to identify miRNAs that are differentially expressed during the early stages of Pi deficiency. Eight small RNA libraries were constructed, and 159 known miRNAs representing 32 miRNA families and 10 novel miRNAs. Members of the miR396 family were extremely abundant. Further, 28 Pi-responsive miRNAs were identified (27 known and 1 novel) of which 8 and 7 were significantly expressed exclusively in leaf and root tissues, respectively. The analysis of Pi-responsive miRNAs target genes suggested that most target genes functioning as transcription factors were involved in root and leaf development. The expression profiles of selected Pi-responsive miRNAs and target genes were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, we discuss the significance of the differences in expression patterns of these miRNAs during the early and later stages of Pi starvation. This study provides useful information concerning the role of miRNAs in response to Pi starvation and will further our understanding of the mechanisms governing Pi homeostasis in maize.
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http://dx.doi.org/10.1111/ppl.12409DOI Listing
June 2016

The interplay between TEAD4 and KLF5 promotes breast cancer partially through inhibiting the transcription of p27Kip1.

Oncotarget 2015 Jul;6(19):17685-97

Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Growing evidence suggests that YAP/TAZ are mediators of the Hippo pathway and promote breast cancer. However, the roles of YAP/TAZ transcription factor partners TEADs in breast cancer remain unclear. Here we found that TEAD4 was expressed in breast cancer cell lines, especially in triple negative breast cancers (TNBC) cell lines. TEAD4 binds to KLF5. Knockdown of either TEAD4 or KLF5 in HCC1937 and HCC1806 cells induced the expression of CDK inhibitor p27. Depletion of either TEAD4 or KLF5 activated the p27 gene promoter and increased the p27 mRNA levels. Depletion of p27 partially prevents growth inhibition caused by TEAD4 and KLF5 knockdown. TEAD4 overexpression stimulated proliferation in vitro and tumor growth in mice, while stable knockdown of TEAD4 inhibited proliferation in vitro and tumor growth in mice. Thus TEAD4 and KLF5, in collaboration, promoted TNBC cell proliferation and tumor growth in part by inhibiting p27 gene transcription. TEAD4 is a potential target and biomarker for the development of novel therapeutics for breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627338PMC
http://dx.doi.org/10.18632/oncotarget.3779DOI Listing
July 2015

Melancholic depression prediction by identifying representative features in metabolic and microarray profiles with missing values.

Pac Symp Biocomput 2015 :455-66

Department of Computer Science and Engineering, Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Tempe, AZ 85287, USA.

Recent studies have revealed that melancholic depression, one major subtype of depression, is closely associated with the concentration of some metabolites and biological functions of certain genes and pathways. Meanwhile, recent advances in biotechnologies have allowed us to collect a large amount of genomic data, e.g., metabolites and microarray gene expression. With such a huge amount of information available, one approach that can give us new insights into the understanding of the fundamental biology underlying melancholic depression is to build disease status prediction models using classification or regression methods. However, the existence of strong empirical correlations, e.g., those exhibited by genes sharing the same biological pathway in microarray profiles, tremendously limits the performance of these methods. Furthermore, the occurrence of missing values which are ubiquitous in biomedical applications further complicates the problem. In this paper, we hypothesize that the problem of missing values might in some way benefit from the correlation between the variables and propose a method to learn a compressed set of representative features through an adapted version of sparse coding which is capable of identifying correlated variables and addressing the issue of missing values simultaneously. An efficient algorithm is also developed to solve the proposed formulation. We apply the proposed method on metabolic and microarray profiles collected from a group of subjects consisting of both patients with melancholic depression and healthy controls. Results show that the proposed method can not only produce meaningful clusters of variables but also generate a set of representative features that achieve superior classification performance over those generated by traditional clustering and data imputation techniques. In particular, on both datasets, we found that in comparison with the competing algorithms, the representative features learned by the proposed method give rise to significantly improved sensitivity scores, suggesting that the learned features allow prediction with high accuracy of disease status in those who are diagnosed with melancholic depression. To our best knowledge, this is the first work that applies sparse coding to deal with high feature correlations and missing values, which are common challenges in many biomedical applications. The proposed method can be readily adapted to other biomedical applications involving incomplete and high-dimensional data.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299923PMC
April 2016

Sparse generalized functional linear model for predicting remission status of depression patients.

Pac Symp Biocomput 2014 :364-75

Department of Computer Science and Engineering, Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.

Complex diseases such as major depression affect people over time in complicated patterns. Longitudinal data analysis is thus crucial for understanding and prognosis of such diseases and has received considerable attention in the biomedical research community. Traditional classification and regression methods have been commonly applied in a simple (controlled) clinical setting with a small number of time points. However, these methods cannot be easily extended to the more general setting for longitudinal analysis, as they are not inherently built for time-dependent data. Functional regression, in contrast, is capable of identifying the relationship between features and outcomes along with time information by assuming features and/or outcomes as random functions over time rather than independent random variables. In this paper, we propose a novel sparse generalized functional linear model for the prediction of treatment remission status of the depression participants with longitudinal features. Compared to traditional functional regression models, our model enables high-dimensional learning, smoothness of functional coefficients, longitudinal feature selection and interpretable estimation of functional coefficients. Extensive experiments have been conducted on the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set and the results show that the proposed sparse functional regression method achieves significantly higher prediction power than existing approaches.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912187PMC
August 2014

RNF115/BCA2 E3 ubiquitin ligase promotes breast cancer cell proliferation through targeting p21Waf1/Cip1 for ubiquitin-mediated degradation.

Neoplasia 2013 Sep;15(9):1028-35

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.

The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has previously been reported to be overexpressed in estrogen receptor α (ERα)-positive breast tumors and to promote breast cell proliferation; however, its mechanism is unknown. In this study, we demonstrated that silencing of BCA2 by small interfering RNAs (siRNAs) in two ERα-positive breast cancer cell lines, MCF-7 and T47D, decreases cell proliferation and increases the protein levels of the cyclin-dependent kinase inhibitor p21Waf/Cip1. The protein stability of p21 was negatively regulated by BCA2. BCA2 directly interacts with p21 and promotes p21 ubiquitination and proteasomal degradation. Knockdown of p21 partially rescues the cell growth arrest induced by the BCA2 siRNA. These results suggest that BCA2 promotes ERα-positive breast cancer cell proliferation at least partially through downregulating the expression of p21.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769882PMC
http://dx.doi.org/10.1593/neo.13678DOI Listing
September 2013

[Reconstruction of large genomic segment coding for human immunoglobulin kappa chain by meiotic homologous recombination of yeast artificial chromosome].

Shi Yan Sheng Wu Xue Bao 2003 Apr;36(2):130-6

Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Sciences, Shanghai Cel-star Institude of Biotechnology, Shanghai.

Meiotic homologous recombination between overlapping yeast artificial chromosome (YAC) can be used to reconstruct larger genomic segment in vivo. We have screened CEPH and Olson human genomic YAC libraries and obtained two YAC clones containing the large genomic segments coding for partial human Ig kappa. In order to reconstruct whole gene cluster of human Ig kappa, two yeast cells containing the different YAC described over were mated and induced to undergo meiotic division and sporulation. Analyzing the results of PCR and Southern blotting, we obtained a clone containing a single recombinant YAC with 400 kb in length, which spans almost the entire gene cluster of human Ig kappa, including 32 V kappa, 5 J kappa, constant domain genes. Besides, we have improved and simplified the traditional method of meiotic recombination between overlapping YACs, and the results indicate the feasibility of this method to reconstruct any larger intact genomic segments.
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April 2003
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