Yue-Qin Chen

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (49)283.59 Total impact

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    ABSTRACT: Acute promyelocytic leukemia (APL) is characterized by the t(15;17)-associated PML-RARA fusion gene. We have previously found that MIR125B1 is highly expressed in patients with APL and may be associated with disease pathogenesis; however, the mechanism by which MIR125B1 exerts its oncogenic potential has not been fully elucidated. Here, we demonstrated that MIR125B1 abundance correlates with the PML-RARA status. MIR125B1 overexpression enhanced PML-RARA expression and inhibited the ATRA-induced degradation of the PML-RARA oncoprotein. RNA-seq analysis revealed a direct link between the PML-RARA degradation pathway and MIR125B1-arrested differentiation. We further demonstrated that the MIR125B1-mediated blockade of PML-RARA proteolysis was regulated via an autophagy-lysosomal pathway, contributing to the inhibition of APL differentiation. Furthermore, we identified DRAM2 (DNA-damage regulated autophagy modulator 2), a critical regulator of autophagy, as a novel target that was at least partly responsible for the function of MIR125B1 involved in autophagy. Importantly, the knockdown phenotypes for DRAM2 are similar to the effects of overexpressing MIR125B1 as impairment of PML-RARA degradation, inhibition of autophagy, and myeloid cell differentiation arrest. These effects of MIR125B1 and its target DRAM2 were further confirmed in an APL mouse model. Thus, MIR125B1 dysregulation may interfere with the effectiveness of ATRA-mediated differentiation through an autophagy-dependent pathway, representing a novel potential APL therapeutic target.
    Autophagy 07/2014; 10(10). · 12.04 Impact Factor
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    ABSTRACT: Long non-coding RNAs (lncRNAs) have been recently found to be pervasively transcribed in human genome and link to diverse human diseases. However, the expression patterns and regulatory roles of lncRNAs in hematopoietic malignancies have not been reported. Here, we carried out a genome-wide lncRNA expression study in MLL-rearranged acute lymphoblastic leukemia (MLL-r ALL) and established lncRNA/mRNA coexpression networks to gain insight into the biological roles of these dysregulated lncRNAs. We detected a number of lncRNAs that were differentially expressed in MLL-r ALL samples compared with MLL-r wild type and identified unique lncRNA expression patterns between MLL-r subtypes with different translocations as well as between infant MLL-r ALL with other MLL-r ALL patients, suggesting that they might be served as novel biomarkers for the disease. Importantly, several lncRNAs that correspond with membrane protein genes, including a lysosome-associated membrane protein, were identified. No such link between the membrane proteins and MLL-r leukemia has been reported previously. Impressively, the functional analysis showed that several lncRNAs corresponded to the expression of MLL-fusion protein target genes, including HOXA9 and MEIS1, etc., while some other associated with histone-related functions or membrane proteins. Further experiments characterize the effect of some lncRNAs on MLL-r leukemia apoptosis and proliferation as the function of the co-expressed HOXA gene cluster. Finally, a set of lncRNAs epigenetically regulated by H3K79 methylation were also discovered. These findings may provide novel insights into the mechanisms of lncRNAs involved in the initiation of MLL-r leukemia. This is the first study linking lncRNAs to leukemogenesis.
    Human Molecular Genetics 01/2014; · 7.69 Impact Factor
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    ABSTRACT: The purpose of this study was to detect the serum microRNAs (miRNAs) that are differentially expressed in cervical squamous cell carcinoma (SCC) patients and negative controls, with a focus on the miRNA profiles of the patients before and after surgery. The aim of the study is to evaluate the potential of these miRNAs as novel markers for the post-therapeutic monitoring of cervical SCC patients. A total of 765 serum miRNAs from 10 cervical SCC patients before surgery, 10 SCC patients after surgery, and 10 negative controls were profiled using a TaqMan MicroRNA Array. A set of selected differentially expressed miRNAs were further analyzed in the patients at different perioperative periods, including preoperative, 1 week postoperative, and one month postoperative. The results showed that several serum miRNAs were differentially expressed in the cervical SCC patients compared with the negative controls, including miR-646, miR-141* and miR-542-3p. More importantly, we found that levels of specific serum miRNAs were deregulated in the pre- and postoperative stages, and these miRNAs could be useful for post-therapeutic monitoring of disease progression. Finally, we depicted a regulatory network of differentially expressed serum miRNAs, and many possible target genes were predicted in the estrogen-mediated signal pathways, supporting the hypothesis that cervical SCC is a hormone-associated gynecological disease. Our study demonstrated that the circulating miRNAs miR-646, miR-141* and miR-542-3p could potentially serve as non-invasive biomarkers for cervical SCC. The levels of these specific miRNAs might be useful for the post-therapeutic monitoring of disease progression. This is the first report showing that circulating miRNAs could serve as biomarkers for the therapeutic intervention of cervical SCC.
    Journal of Hematology & Oncology 01/2014; 7(1):6. · 4.46 Impact Factor
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    ABSTRACT: MicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has been reported to be downregulated in human colorectal carcinoma (CRC) when compared to adjacent non-tumor tissue. However, its diagnostic value and role in CRC have yet to be described. CXC chemokine receptor-4 (CXCR4), which participates in multiple cell processes such as cell invasion-related signaling pathways, was predicted to be a potential target of miR-133b. The aim of this study was to investigate the associations and functions of miR-133b and CXCR4 in CRC initiation and invasion. Mature miR-133b and CXCR4 expression levels were detected in 31 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 6 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate CXCR4 as a putative target gene of miR-133b. Regulation of CXCR4 expression by miR-133b was assessed using qRT-PCR and Western blot analysis, and the effects of exogenous miR-133b and CXCR4 on cell invasion and migration were evaluated in vitro using the SW-480 and SW-620 CRC cell lines. A significant downregulation of miR-133b was observed in 93.55% of CRC tissues, and the expression of miR-133b was much lower in metastatic tumors (stage C and D, stratified by the Modified Dukes Staging System) than in primary tumors (stage A and B). In contrast, CXCR4 protein expression significantly increased in 52.63% of CRC samples, and increased CXCR4 expression in CRC was associated with advanced tumor stage. CXCR4 was shown to be a direct target of miR-133b by luciferase reporter assays, and transfection of miR-133b mimics inhibited invasion and stimulated apoptosis of SW-480 and SW-620 CRC cells. Our study demonstrated that downregulated miR-133b contributed to increased cell invasion and migration in CRC by negatively regulating CXCR4. These findings may be significant for the development of therapy target for CRC.
    Molecular Cancer 12/2013; 12(1):164. · 5.13 Impact Factor
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    ABSTRACT: Increasing grain yields is a major focus of crop breeders around the world. Here we report that overexpression of the rice microRNA (miRNA) OsmiR397, which is naturally highly expressed in young panicles and grains, enlarges grain size and promotes panicle branching, leading to an increase in overall grain yield of up to 25% in a field trial. To our knowledge, no previous report has shown a positive regulatory role of miRNA in the control of plant seed size and grain yield. We determined that OsmiR397 increases grain yield by downregulating its target, OsLAC, whose product is a laccase-like protein that we found to be involved in the sensitivity of plants to brassinosteroids. As miR397 is highly conserved across different species, our results suggest that manipulating miR397 may be useful for increasing grain yield not only in rice but also in other cereal crops.
    Nature Biotechnology 07/2013; · 32.44 Impact Factor
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    Yu-Meng Sun, Kang-Yu Lin, Yue-Qin Chen
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    ABSTRACT: MicroRNAs (miRNAs) are emerging as a novel class of non-coding RNA molecules that regulate gene expression at a post-transcriptional level. More than 1000 miRNAs have been identified in human cells to date, and they are reported to play important roles in normal cell homeostasis, cell metastasis and disease pathogensis and progression. MiR-125, which is a highly conserved miRNA throughout diverse species from nematode to humans, consists of three homologs hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125-2. Members of this family have been validated to be down-regulated, exhibiting its disease-suppressing properties in many different types of diseases, while they also have disease-promoting functions in certain contexts. MiR-125 targets a number of genes such as transcription factors, matrix-metalloprotease, members of Bcl-2 family and others, aberrance of which may lead to abnormal proliferation, metastasis and invasion of cells, even carcinomas. Furthermore, miR-125 plays a crucial role in immunological host defense, especially in response to bacterial or viral infections. In this review, we summarize the implication of miR-125 family in disease suppression and promotion, focusing on carcinoma and host immune responses. We also discussed the potential of this miRNA family as promising biomarkers and therapeutic targets for different diseases in future.
    Journal of Hematology & Oncology 01/2013; 6(1):6. · 4.46 Impact Factor
  • Bo-Wei Han, Yue-Qin Chen
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    ABSTRACT: Differential abundance and activity of long noncoding RNAs (lncRNAs) are recognized as the hallmark features in various diseases. We highlight the lncRNAs that play a functional role in the development of blood cells. Many lncRNAs and the protein complexes within which they interact have been implicated in various types of cancers. Multiple lncRNAs participate in normal and may be implicated in malignant hematopoiesis associated with blood cell cancers, such as leukemia, by regulating gene expression through such mechanisms as redirecting chromatin remodeling complexes and activating epigenetic silencing, either of which can inactivate tumor suppressor genes or activate oncogenes. Because of their potential importance in cancers of the blood, lncRNAs may be useful as diagnostic and prognostic markers, and it may be possible to develop lncRNA-mediated therapy.
    Science Signaling 01/2013; 6(289):re5. · 7.65 Impact Factor
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    ABSTRACT: Context:There is currently no reliable noninvasive biomarker for the clinical diagnosis of endometriosis. Previous analyses have reported that circulating microRNAs (miRNAs) can serve as biomarkers for a number of diseases.Objective:The study aims to detect the serum miRNAs that are differentially expressed between endometriosis patients and negative controls to evaluate the potential of these miRNAs as diagnostic markers for endometriosis.Design:A total of 765 serum miRNAs were profiled using a TaqMan microRNA array in a pool of 10 endometriosis patients and a pool of 10 negative controls, and a set of selected miRNAs were further analyzed in a validation cohort consisting of sera from 60 patients and 25 controls including 10 samples used in array profiling.Results:The relative expression levels of miR-199a and miR-122 were found to be up-regulated in endometriosis patient samples compared with control samples, whereas miR-145*, miR-141*, miR-542-3p, and miR-9* were down-regulated in endometriosis patients. Importantly, the relative expression of miR-199a (P < 0.05) and miR-122 can be used to discriminate between severe and mild endometriosis. We also found that miR-199a is well correlated with pelvic adhesion and lesion distribution (P < 0.05) and associated with hormone-mediated signaling pathways. Furthermore, we investigated the diagnostic value of these molecules and confirmed the optimal combination of miR-199a, miR-122, miR-145*, and miR-542-3p with area under the curve of 0.994 (95% confidence interval = 0.984-1.000, P < 0.001) and a cutoff point (0.4950) of 93.22% sensitivity and 96.00% specificity.Conclusions:Our study demonstrated that the circulating miRNAs miR-199a, miR-122, miR-145*, and miR-542-3p could potentially serve as noninvasive biomarkers for endometriosis. miR-199a may also play an important role in the progression of the disease. This is the first report that circulating miRNAs serve as biomarkers of endometriosis.
    The Journal of clinical endocrinology and metabolism 11/2012; · 6.50 Impact Factor
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    ABSTRACT: Camptothecin (CPT) is an effective chemotherapeutic agent for treatment of patients with cancer. The mechanisms underlying CPT-mediated responses in cancer cells are not fully understood. MicroRNA (miRNA) play important roles in tumorigenesis and drug sensitivity. However, the interaction between camptothecin and miRNA has not been previously explored. In this study, we verified that miR-125b was down-regulated in CPT-induced apoptosis in cancer cells and that ectopic expression of miR-125b partially restored cell viability and inhibited cell apoptosis that was induced by CPT. In addition, we demonstrated that CPT induced apoptosis in cancer cells by miR-125b-mediated mitochondrial pathways via targeting to the 3'-untranslated (UTR) regions of Bak1, Mcl1, and p53. A significant increase in Bak1, Mcl1, and p53 protein levels was detected in response to the treatments of CPT. It is noteworthy that the expression levels of Bak1, Mcl1, and p53 increased in a time-dependent manner and negatively correlated with miR-125b expression. It is noteworthy that we revealed that miR-125b directly targeted the 3'UTR regions of multiple genes in a CPT-induced mitochondrial pathway. In addition, most targets of miR-125b were proapoptotic genes, whereas some of the targets were antiapoptotic genes. We hypothesized that miR-125b may mediate the activity of chemotherapeutic agents to induce apoptosis by regulating multiple targets. This is the first report to show that camptothecin induces cancer cell apoptosis via miRNA-mediated mitochondrial pathways. The results suggest that suppression of miR-125b may be a novel approach for the treatment of cancer.
    Molecular pharmacology 01/2012; 81(4):578-86. · 4.53 Impact Factor
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    ABSTRACT: Relapse is a major challenge in the successful treatment of childhood acute lymphoblastic leukemia (ALL). Despite intensive research efforts, the mechanisms of ALL relapse are still not fully understood. An understanding of the molecular mechanisms underlying treatment outcome, therapy response and the biology of relapse is required. In this study, we carried out a genome-wide microRNA (miRNA) microarray analysis to determine the miRNA expression profiles and relapse-associated miRNA patterns in a panel of matched diagnosis-relapse or diagnosis-complete remission (CR) childhood ALL samples. A set of miRNAs differentially expressed either in relapsed patients or at diagnosis compared with CR was further validated by quantitative real-time polymerase chain reaction in an independent sample set. Analysis of the predicted functions of target genes based on gene ontology 'biological process' categories revealed that the abnormally expressed miRNAs are associated with oncogenesis, classical multidrug resistance pathways and leukemic stem cell self-renewal and differentiation pathways. Several targets of the miRNAs associated with ALL relapse were experimentally validated, including FOXO3, BMI1 and E2F1. We further investigated the association of these dysregulated miRNAs with clinical outcome and confirmed significant associations for miR-708, miR-223 and miR-27a with individual relapse-free survival. Notably, miR-708 was also found to be associated with the in vivo glucocorticoid therapy response and with disease risk stratification. These miRNAs and their targets might be used to optimize anti-leukemic therapy, and serve as novel targets for development of new countermeasures of leukemia. This fundamental study may also contribute to establish the mechanisms of relapse in other cancers.
    Human Molecular Genetics 09/2011; 20(24):4903-15. · 7.69 Impact Factor
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    ABSTRACT: MicroRNA-125b (miR-125b), a small noncoding RNA molecule, has been found to be deregulated and functions as an oncogene in many cancers including hematopoietic malignancies. However, the mechanisms accounting for miR-125b dysregulation remain to be elucidated. The present study aims to identify the factors that might contribute to up-regulation of miR-125b in human hematopoietic malignancies and its downstream targets for lineage-specific differentiation. We at first reported that CDX2, a homeobox transcription factor, binds to promoter regions of the miR-125b gene and activates transcriptional regulation of miR-125b in malignant myeloid cells. We further revealed that increasing levels of CDX2 in malignant myeloid cells activate miR-125b expression, which in turn inhibits core binding factor β (CBFβ) translation, thereby counteracting myeloid cell differentiation, at least for granulocytic lineage, and promoting leukemogenesis. Interestingly, we found that this novel pathway including CDX2, miR-125b, and CBFβ was mediated by undergoing all-trans-retinoic acid induction. Once differentiation ensues with all-trans-retinoic acid treatment, CDX2 activity decreases, leading to a reduction in miR-125b transcription and up-regulation of CBFβ in myeloid cells and in patients. The study provides a new mechanism that contributes to hematopoietic malignancies, which could involve deregulation of miR-125b and its up- and downstream factors. As altered expression of miRNAs has been reported in a wide range of malignancies, delineating the underlying molecular mechanisms of aberrant miRNA expression and characterizing the upstream and downstream factors will help to understand important steps in the pathogenesis of these afflictions.
    Journal of Biological Chemistry 09/2011; 286(44):38253-63. · 4.65 Impact Factor
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    ABSTRACT: Although current chemotherapy regimens have remarkably improved the cure rate of pediatric acute promyelocytic leukemia (APL) over the past decade, more than 20% of patients still die of the disease, and the 5-year cumulative incidence of relapse is 17%. The precise gene pathways that exert critical control over the determination of cell lineage fate during the development of pediatric APL remain unclear. In this study, we analyzed miR-125b expression in 169 pediatric acute myelogenous leukemia (AML) samples including 76 APL samples before therapy and 38 APL samples after therapy. The effects of enforced expression of miR-125b were evaluated in leukemic cell and drug-resistant cell lines. miR-125b is highly expressed in pediatric APL compared with other subtypes of AML and is correlated with treatment response, as well as relapse of pediatric APL. Our results further demonstrated that miR-125b could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor BCL2-antagonist/killer 1 (Bak1). Remarkably, miR-125b was also found to be up-regulated in leukemic drug-resistant cells, and transfection of a miR-125b duplex into AML cells can increase their resistance to therapeutic drugs, These findings strongly indicate that miR-125b plays an important role in the development of pediatric APL at least partially mediated by repressing BAK1 protein expression and could be a potential therapeutic target for treating pediatric APL failure.
    Molecular Cancer 09/2011; 10:108. · 5.13 Impact Factor
  • Cong-Ying Wang, Yue-Qin Chen, Qing Liu
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    ABSTRACT: The whole structure of higher plants is generated dynamically throughout the life cycle by the activity of stem cell niches at the apex of shoot and root. Hormone molecules and many transcription factors cooperate to balance the stem cell maintenance and differentiation. It is becoming increasingly clear that microRNA (miRNA) molecules are also participants in these processes. Here, we highlight the advances that have been made in regarding the roles of miRNAs in plant stem cell control. These advances provide a framework for our understanding of how signals are integrated to specify and position the stem cell niches in plants.
    Biochemical and Biophysical Research Communications 06/2011; 409(3):363-6. · 2.41 Impact Factor
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    ABSTRACT: Small RNAs constitute a new and unanticipated layer of gene regulation present in the three domains of life. In plants, all organs are ultimately derived from a few pluripotent stem cells localized in specialized structures called apical meristems. The development of meristems involves a coordinated balance between undifferentiated growth and differentiation, a phenomenon requiring a tight regulation of gene expression. We used in vitro cultured embryogenic calli as a model to investigate the roles of meristem-associated small RNAs. Using high throughput sequencing, we sequenced 20 million short reads with size of 18-30 nt from rice undifferentiated and differentiated calli. We confirmed 50 known microRNA families, representing one third of annotated rice microRNAs. Using a specific computational pipeline for plant microRNA identification, we identified 24 novel microRNA families. Among them, 53 microRNA or microRNA* sequences appear to vary in expression between differentiated and undifferentiated calli, suggesting a role in meristem development. Our analysis also revealed a new class of plant small RNAs derived from 5' or 3' ends of mature tRNA analogous to the tRFs in human cancer cell. We independently verified the expression of these small RNAs from 5' end of mature tRNA using qRT-PCR.
    RNA biology 05/2011; 8(3):538-47. · 5.56 Impact Factor
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    ABSTRACT: Plant genomes have undergone multiple rounds of duplications that contributed massively to the growth of gene families. The structure of resulting families has been studied in depth for protein-coding genes. However, little is known about the impact of duplications on noncoding RNA (ncRNA) genes. Here we perform a systematic analysis of duplicated regions in the rice genome in search of such ncRNA repeats. We observe that, just like their protein counterparts, most ncRNA genes have undergone multiple duplications that left visible sequence conservation footprints. The extent of ncRNA gene duplication in plants is such that these sequence footprints can be exploited for the discovery of novel ncRNA gene families on a large scale. We developed an SVM model that is able to retrieve likely ncRNA candidates among the 100,000+ repeat families in the rice genome, with a reasonably low false-positive discovery rate. Among the nearly 4000 ncRNA families predicted by this means, only 90 correspond to putative snoRNA or miRNA families. About half of the remaining families are classified as structured RNAs. New candidate ncRNAs are particularly enriched in UTR and intronic regions. Interestingly, 89% of the putative ncRNA families do not produce a detectable signal when their sequences are compared to another grass genome such as maize. Our results show that a large fraction of rice ncRNA genes are present in multiple copies and are species-specific or of recent origin. Intragenome comparison is a unique and potent source for the computational annotation of this major class of ncRNA.
    RNA 03/2011; 17(3):390-400. · 5.09 Impact Factor
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    ABSTRACT: We scanned 18S rDNA environmental clone libraries constructed from the South China Sea samples and found four libraries that contained radiolarian-affiliated sequences. Comparing them with available data from elsewhere in the open sea, we discovered a high number of novel radiolarian sequences in the South China Sea. These novel radiolarian sequences were clustered together in the phylogenetic tree, indicating the existence of several unique biogeographical groups forming two new clades.
    Palaeoworld 01/2011; 20:252-256.
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    ABSTRACT: Multidrug resistance (MDR) and disease relapse are challenging clinical problems in the treatment of leukaemia. Relapsed disease is frequently refractory to chemotherapy and exhibits multiple drug resistance. Therefore, it is important to identify the mechanism by which cancer cells develop resistance. In this study, we used microRNA (miRNA) microarray and qRT-PCR approaches to investigate the expression of miRNAs in three leukaemia cell lines with different degrees of resistance to doxorubicin (DOX) compared with their parent cell line, K562. The expression of miR-331-5p and miR-27a was inversely correlated with the expression of a drug-resistant factor, P-glycoprotein (P-gp), in leukaemia cell lines with gradually increasing resistance. The development of drug resistance is regulated by the expression of the P-gp. Transfection of the K562 and, a human promyelocytic cell line (HL) HL60 DOX-resistant cells with miR-331-5p and miR-27a, separately or in combination, resulted in the increased sensitivity of cells to DOX, suggesting that correction of altered expression of miRNAs may be used for therapeutic strategies to overcome leukaemia cell resistance. Importantly, miR-331-5p and miR-27a were also expressed at lower levels in a panel of relapse patients compared with primary patients at diagnosis, further illustrating that leukaemia relapse might be a consequence of deregulation of miR-331-5p and miR-27a.
    Journal of Cellular and Molecular Medicine 11/2010; 15(10):2164-75. · 4.75 Impact Factor
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    ABSTRACT: MicroRNA-122 (miR-122) is a liver-specific microRNA whose expression is specifically turned on in the mouse liver during embryogenesis, thus it is expected to be involved in liver development. However, the role of miR-122 in liver development and its potential underlying mechanism remain unclear. Here, we show that the expression of miR-122 is closely correlated with four liver-enriched transcription factors (LETFs)-hepatocyte nuclear factor (HNF) 1α, HNF3β, HNF4α, and CCAAT/enhancer-binding protein (C/EBP) α-in the livers of developing mouse embryos and in human hepatocellular carcinoma (HCC) cell lines. Correspondingly, promoter analysis revealed that these LETFs are coordinately involved in the transcriptional regulation of miR-122, and three HNFs directly bind to the miR-122 promoter as transcriptional activators. Using a luciferase reporter system, we identified a group of miR-122 targets involved in proliferation and differentiation regulation. Among these targets, the most prominently repressed target was CUTL1, a transcriptional repressor of genes specifying terminal differentiation in multiple cell lineages, including hepatocytes. We show that CUTL1 expression is gradually silenced at the posttranscriptional level during mouse liver development. Overexpression and knockdown studies both showed that miR-122 repressed CUTL1 protein expression in HCC cell lines. Finally, we show that the stable restoration of miR-122 in HepG2 cells suppresses cellular proliferation and activates the expression of three hepatocyte functional genes, including the cholesterol-7α hydroxylase gene (CYP7A1), a known target of CUTL1 in hepatocytes. CONCLUSION: Our study provides a model in which miR-122 functions as an effector of LETFs and contributes to liver development by regulating the balance between proliferation and differentiation of hepatocytes, at least by targeting CUTL1.
    Hepatology 10/2010; 52(4):1431-42. · 12.00 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) represent an important class of small non-coding RNAs (sRNAs) that regulate gene expression by targeting messenger RNAs. However, assigning miRNAs to their regulatory target genes remains technically challenging. Recently, high-throughput CLIP-Seq and degradome sequencing (Degradome-Seq) methods have been applied to identify the sites of Argonaute interaction and miRNA cleavage sites, respectively. In this study, we introduce a novel database, starBase (sRNA target Base), which we have developed to facilitate the comprehensive exploration of miRNA-target interaction maps from CLIP-Seq and Degradome-Seq data. The current version includes high-throughput sequencing data generated from 21 CLIP-Seq and 10 Degradome-Seq experiments from six organisms. By analyzing millions of mapped CLIP-Seq and Degradome-Seq reads, we identified ∼1 million Ago-binding clusters and ∼2 million cleaved target clusters in animals and plants, respectively. Analyses of these clusters, and of target sites predicted by 6 miRNA target prediction programs, resulted in our identification of approximately 400,000 and approximately 66,000 miRNA-target regulatory relationships from CLIP-Seq and Degradome-Seq data, respectively. Furthermore, two web servers were provided to discover novel miRNA target sites from CLIP-Seq and Degradome-Seq data. Our web implementation supports diverse query types and exploration of common targets, gene ontologies and pathways. The starBase is available at http://starbase.sysu.edu.cn/.
    Nucleic Acids Research 10/2010; 39(Database issue):D202-9. · 8.28 Impact Factor
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    ABSTRACT: Deposition of collagen IV in proximal tubule cells (PTCs) plays an important role during diabetic nephropathy, but the mechanism underlying excessive production of collagen IV remains poorly understood. In this study, we examined the miRNA profile of HK-2 cells and found that high glucose/TGF-beta1 induced significant down-regulation of miR-29a. We then showed that miR-29a negatively regulated collagen IV by directly targeting the 3'UTRs of col4a1 and col4a2. These results suggest that miR-29a acts as a repressor to fine-tune collagen expression and that the reduction of miR-29a caused by high glucose may increase the risk of excess collagen deposition in PTCs.
    FEBS letters 02/2010; 584(4):811-6. · 3.54 Impact Factor

Publication Stats

1k Citations
283.59 Total Impact Points

Institutions

  • 2009–2014
    • Sun Yat-Sen University
      • State Key Laboratory of Biocontrol
      Shengcheng, Guangdong, China
  • 2002–2008
    • Zhongshan University
      中山, Guangdong, China
  • 2002–2003
    • Guangzhou University
      Peping, Beijing, China