Xiaofei Zheng

Government of the People's Republic of China, Peping, Beijing, China

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Publications (36)126.78 Total impact

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    ABSTRACT: Background Thousands of long noncoding RNAs (lncRNAs) have been reported in mammalian genomes. These RNAs represent an important subset of pervasive genes involved in a broad range of biological functions. Aberrant expression of lncRNAs is associated with many types of cancers. Here, in order to explore the potential lncRNAs involved in hepatocellular carcinoma (HCC) oncogenesis, we performed lncRNA gene expression profile analysis in 3 pairs of human HCC and adjacent non-tumor (NT) tissues by microarray. Methodology Differentially expressed lncRNAs and mRNAs were detected by human lncRNA microarray containing 33,045 lncRNAs and 30,215 coding transcripts. Bioinformatic analyses (gene ontology, pathway and network analysis) were applied for further study of these differentially expressed mRNAs. By qRT-PCR analysis in nineteen pairs of HCC and adjacent normal tissues, we found that eight lncRNAs were aberrantly expressed in HCC compared with adjacent NT tissues, which is consistent with microarray data. Conclusions We identified 214 lncRNAs and 338 mRNAs abnormally expressed in all three HCC tissues (Fold Change ≥2.0, P<0.05 and FDR <0.05) with the genome-wide lncRNAs and mRNAs expression profile analysis. The lncRNA-mRNA co-expression network was constructed, which may be used for predicting target genes of lncRNAs. Furthermore, we demonstrated for the first time that BC017743, ENST00000395084, NR_026591, NR_015378 and NR_024284 were up-regulated, whereas NR_027151, AK056988 and uc003yqb.1 were down-regulated in nineteen pairs of HCC samples compared with adjacent NT samples. Expression of seven lncRNAs was significantly correlated to their nearby coding genes. In conclusion, our results indicated that the lncRNA expression profile in HCC was significantly changed, and we identified a series of new hepatocarcinoma associated lncRNAs. These results provide important insights about the lncRNAs in HCC pathogenesis.
    PLoS ONE 07/2014; 9(7):e101707. DOI:10.1371/journal.pone.0101707 · 3.53 Impact Factor
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    ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide. In this study, we aimed to investigate the underlying mechanisms of metastasis inhibition by miR-205 in ESCC. In microRNA (miRNA) array and quantitative RT-PCR analyses, we found that the expression level of miR-205 was significantly lower in patients with lymph node metastasis compared with that in patients without lymph node metastasis. After transfection of miR-205 mimics or inhibitors into ESCC cell lines, a significant negative correlation was observed between the expression level of miR-205 and Smad1. In luciferase reporter assays, we revealed that miR-205 inhibited the expression of SMAD1 by targeting the 3′ untranslated region (3′-UTR) of SMAD1 mRNA in ESCC cells. Furthermore, our results showed that miR-205 suppressed the invasion and migration of ESCC cells, whereas Smad1 increased their invasion and migration. Taken together, our study demonstrates that miR-205 functions as a suppressor of tumor metastasis by regulating SMAD1 expression through targeting the 3′-UTR of SMAD1 mRNA in ESCC. Therefore, miR-205 may be a potential therapeutic target for miRNA-based therapy of ESCC.
    Chinese Science Bulletin 07/2014; 59(19). DOI:10.1007/s11434-014-0272-z · 1.37 Impact Factor
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    ABSTRACT: Aberrant expression of microRNAs (miRNAs) was reported frequently in different human cancers. The major role of miRNA is targeting 3′-UTR of coding gene and causing translational repression or mRNA degradation. miR-10b overexpression was reported to promote breast cancer metastasis by up-regulating RHOC expression. But its expression in hepatocellular carcinoma (HCC) remains unclear. Our study indicated that the expression of miR-10b was different in HCC and adjacent tissue samples, and reduced expression of miR-10b in HCC was related to vein invasion. High-level expression of RHOC was also related to vein invasion in HCC. But no correlation was found between miR-10b and RHOC expression. These results suggest that miR-10b and RHOC are independent predictors of HCC invasion and metastasis.
    Chinese Science Bulletin 07/2014; 59(19):2249-2253. DOI:10.1007/s11434-014-0271-0 · 1.37 Impact Factor
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    ABSTRACT: Accumulating evidence suggests that microRNAs (miRNAs) can function as oncogenes or as tumor suppressor genes depending on the tissue type or target. Therefore, clarification of the specific roles of miRNAs is vital for the diagnosis and treatment of cancer. In the present study, miR-451 was found to be downregulated in hepatocellular carcinoma (HCC) tissues when compared to that in adjacent tissues. Functional analysis showed that, in vitro, miR-451 inhibited the migration of hepatoma cell lines HepG2 and SK-Hep-1. Further investigation of the molecular mechanisms identified activating transcription factor 2 (ATF2) as a target of miR-451. miR-451 inhibited ATF2 expression by binding to the 3'UTR. An in vivo assay revealed a significant negative correlation between miR-451 and ATF2 in liver cancer tissues. According to previous findings reported in the literature, the opposing functions of ATF2 are related to its subcellular localization. In the nucleus, ATF2 displays oncogenic activities in melanoma. In the present study, ATF2 exhibited a higher expression level in the nucleus in tumoral tissues of HCC as detected by immunohistochemistry. In conclusion, in this study, we identified a potential target of miR-451, ATF2, and revealed a novel role of miR-451 in the inhibition of the migratory ability of hepatoma cell lines.
    Oncology Reports 06/2014; 32(3). DOI:10.3892/or.2014.3296 · 2.19 Impact Factor
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    ABSTRACT: Eye absent (Eya) proteins are involved in cell fate determination in a broad spectrum of cells and tissues. Aberrant expression of Eya2 has been documented in a variety of cancers and correlates with clinical outcome. However, whether microRNAs (miRNAs) can regulate Eya2 expression remains unknown. Here, we show that miR-30a represses Eya2 expression by binding to the 3’-untranslated region of Eya2. Overexpression of Eya2 in miR-30a-transfected breast cancer cells effectively rescued the inhibition of cell proliferation and migration caused by miR-30a. Knockdown of Eya2 by small-interfering RNA (siRNA) in breast cancer cells mimicked the effect induced by miR-30a and abolished the ability of miR-30a to regulate breast cancer cell proliferation and migration. The miR-30a/Eya2 axis could regulate G1/S cell cycle progression, accompanied by the modulation of expression of cell cycle-related proteins, including cyclin A, cyclin D1, cyclin E, and c-Myc. Moreover, miR-30a expression was downregulated in breast cancer patients, and negatively correlated with Eya2, which was upregulated in breast cancer patients. These data suggest that the miR-30a/Eya2 axis may play an important role in breast cancer development and progression and that miR-30a activation or Eya2 inhibition may be a useful strategy for cancer treatment.
    Biochemical and Biophysical Research Communications 03/2014; 445(2). DOI:10.1016/j.bbrc.2014.01.174 · 2.28 Impact Factor
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    ABSTRACT: Loss or attenuated expression of the tumor suppressor gene FHIT is associated paradoxically with poor progression of human tumors. Fhit promotes apoptosis and regulates reactive oxygen species, however, the mechanism by which Fhit inhibits tumor growth in animals remains unclear. In this study, we used a multi-discliplinary approach based on bioinformatics, small RNA library screening, human tissue analysis and a xenograft mouse model to identify a novel member of the miR-548 family in the fourth intron of the human FHIT gene. Characterization of this human-specific microRNA illustrates the importance of this class of microRNAs in tumor suppression and may influence interpretation of Fhit action in human cancer.
    Cancer Research 02/2014; 74(8). DOI:10.1158/0008-5472.CAN-13-3279 · 9.28 Impact Factor
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    ABSTRACT: An increasing data indicates that altered microRNAs (miRNAs) participate in the radiation-induced DNA damage response. However, a correlation of mRNA and miRNA profiles across the entire genome and in response to irradiation has not been thoroughly assessed. We analyzed miRNA microarray data collected from HeLa cells after ionizing radiation (IR), quantified the expression profiles of mRNAs and performed comparative analysis of the data sets using target prediction algorithms, Gene Ontology (GO) analysis, pathway analysis, and gene network construction. The results showed that the altered miRNAs were involved in regulation of various cellular functions. miRNA-gene network analyses revealed that miR-186, miR-106b, miR-15a/b, CCND1 and CDK6 played vital role in the cellular radiation response. Using qRT-PCR, we confirmed that twenty-two miRNAs showed differential expression in HeLa cells treated with IR and some of these miRNAs affected cell cycle progression. This study demonstrated that miRNAs influence gene expression in the entire genome during the cellular radiation response and suggested vital pathways for further research.
    Chinese Science Bulletin 12/2013; 58(36). DOI:10.1007/s11434-013-6033-6 · 1.37 Impact Factor
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    ABSTRACT: Long non-coding RNAs (lncRNAs), which represent a new frontier in molecular biology, play important roles in regulating gene expression at epigenetic, transcriptional and post-transcriptional levels. More and more lncRNAs have been found to play important roles in normal cell physiological activities, and participate in the development of varieties of tumors and other diseases. Previously, we have only been able to determine the function of lncRNAs through multiple mechanisms, including genetic imprinting, chromatin remodeling, splicing regulation, mRNA decay, and translational regulation. Application of technological advances to research into the function of lncRNAs is extremely important. The major tools for exploring lncRNAs include microarrays, RNA sequencing (RNA-seq), Northern blotting, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), RNA interference (RNAi), RNA-binding protein immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP), crosslinking-immunopurification (CLIP), and bioinformatic prediction. In this review, we highlight the functions of lncRNAs, and advanced methods to research lncRNA-protein interactions.
    Science China. Life sciences 10/2013; 56(10):876-885. DOI:10.1007/s11427-013-4553-6 · 1.51 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) have been shown to be dysregulated in virus-related cancers; however, miRNA regulation of virus-related cancer development and progression remains poorly understood. Here, we report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote cancer growth and metastasis in a mouse model of hepatocellular carcinoma (HCC). Hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is an important regulator of cancer cell growth. We used miRNA target prediction programs to identify miR-148a as a regulator of HPIP. Expression of miR-148a in hepatoma cells reduced HPIP expression, leading to repression of AKT and ERK and subsequent inhibition of mTOR through the AKT/ERK/FOXO4/ATF5 pathway. HBx has been shown to play a critical role in the molecular pathogenesis of HBV-related HCC. We found that HBx suppressed p53-mediated activation of miR-148a. Moreover, expression of miR-148a was downregulated in patients with HBV-related liver cancer and negatively correlated with HPIP, which was upregulated in patients with liver cancer. In cultured cells and a mouse xenograft model, miR-148a reduced the growth, epithelial-to-mesenchymal transition, invasion, and metastasis of HBx-expressing hepatocarcinoma cells through inhibition of HPIP-mediated mTOR signaling. Thus, miR-148a activation or HPIP inhibition may be a useful strategy for cancer treatment.
    The Journal of clinical investigation 01/2013; 123(2). DOI:10.1172/JCI64265 · 13.77 Impact Factor
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    ABSTRACT: In this study, we explored the possibility of SOX17 promoter region methylation as an esophageal cancer detection marker, the regulation of SOX17 expression, and the function of SOX17 in the WNT signaling pathway in esophageal cancer. Eight esophageal cancer cell lines, 9 normal esophageal mucosa samples, 60 cases of dysplasia, and 169 cancer tissue samples were included. Methylation-specific PCR, semiquantitative reverse transcription-PCR, immunohistochemistry, luciferase reporter assay, colony formation, and Western blot analysis were used to analyze methylation and function of SOX17 in esophageal cancer. MicroRNA-related detection methods were performed to evaluate microRNA regulation of SOX17. SOX17 methylation was found in progression tendency with 0% of normal mucosa, 39% of grade 1 dysplasia, 48% of grades 2 and 3 dysplasia, and 65% of primary cancer. SOX17 methylation is related to esophageal cancer patients' history of alcohol use and may induce β-catenin expression and redistribution. Loss of SOX17 expression is correlated to promoter region hypermethylation, and re-expression was activated by 5-aza-2'-deoxycytidine treatment in esophageal cancer cell lines. Restoration of SOX17 expression suppresses TCF/β-catenin-dependent transcription and colony formation. MicroRNA 141 was also found to down-regulate SOX17 expression and activate the WNT signal pathway. SOX17 is frequently methylated in esophageal cancer and in a progression tendency during esophageal carcinogenesis. Loss of SOX17 removes the normal inhibition of WNT signaling and promotes esophageal tumorigenesis.
    The Journal of molecular diagnostics: JMD 08/2012; 14(6):577-85. DOI:10.1016/j.jmoldx.2012.06.004 · 3.96 Impact Factor
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    ABSTRACT: Cisplatin is a classic chemotherapy agent used for treating human non-small cell lung cancer (NSCLC). However, cisplatin resistance is a challenge against successful clinical use. Glutathione S-transferase P1 (GSTP1) has been reported to contribute to cisplatin resistance in many studies. MicroRNAs (miRNAs) are short non-coding RNAs that are 21-25 nucleotides in length. They play a role in post-transcriptional gene regulation by inducing repression and/or mRNA degradation. Recent studies have shown that miRNAs are responsible for cisplatin resistance. This study aims to determine whether deregulated miRNAs can sensitize human lung adenocarcinoma cells to cisplatin by targeting GSTP1. Real-time RT-PCR revealed that GSTP1 mRNA expression was 2.7 ± 0.38 folds (p=0.039) upregulated in A549/CDDP cells, compared with the parental A549 cells, while miR-513a-3p expression was 0.34 ± 0.03 folds (p=0.023) downregulated. Luciferase activity assay proved that GSTP1 was a target gene of miR-513a-3p, which was confirmed by Western blot analysis. Furthermore, CCK-8 assay showed that overexpression of miR-513a-3p could enhance cisplatin-induced apoptosis in human lung adenocarcinoma cell lines, A549/CDDP and SPC-A-1. In conclusion, our data demonstrated that miR-513a-3p can sensitize human lung adenocarcinoma cells to cisplatin by targeting GSTP1.
    Lung cancer (Amsterdam, Netherlands) 06/2012; 77(3):488-94. DOI:10.1016/j.lungcan.2012.05.107 · 3.74 Impact Factor
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    ABSTRACT: MicroRNAs may function to promote or suppress tumor development, depending on the cellular context. The important role of microRNAs in regulating molecular pathways underlying tumorigenesis has been emphasized in hepatocellular carcinoma (HCC). MicroRNAs regulate gene expression via post-transcriptional mechanisms by inhibiting translation or by degrading mRNA. In this study, we show that microRNA-1 (miR-1) and microRNA-499 (miR-499) are capable of repressing the expression of the ets1 proto-oncogene, which plays a fundamental role in the extracellular matrix (ECM) degradation, a process required for tumor cell invasion and migration. We used luciferase reporter assays to demonstrate that miR-1 and miR-499 target the 3' untranslated region (UTR) of ets1. Overexpression of miR-1 and miR-499 in HepG2 cells led to downregulation of ets1 mRNA and protein as assessed by quantitative reverse transcription PCR and western blot analysis. Furthermore, overexpression of miR-1 and miR-499 inhibited the invasion and migration of HepG2 cells in matrigel invasion and transwell migration assays, respectively. These results suggest that miR-1 and miR-499 may play an important role in the pathogenesis of HCC by regulating ets1.
    Oncology Reports 06/2012; 28(2):701-6. DOI:10.3892/or.2012.1850 · 2.19 Impact Factor
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    ABSTRACT: Valosin containing protein (VCP)/p97 plays various important roles in cells. Moreover, elevated expression of VCP in hepatocellular carcinoma (HCC) is correlated with increased incidence of recurrence. But the role of VCP in HCC progression in vitro and in vivo is unclear. And there are few reports about the regulation mechanism on the expression of VCP in HCC. In this study, it was identified that the level of VCP was frequently increased in human HCC tissues. In addition, down-regulation of VCP with siRNAs could dramatically suppress the genesis and progression of tumor in vivo. It was found that miR-129-5p directly inhibited the expression of VCP in several HCC cell lines. Meanwhile, the level of VCP in HCC tissues was negatively associated with the level of miR-129-5p. Our further investigation showed that the enhanced expression of miR-129-5p also suppressed tumor growth in vivo. Moreover, it was revealed that miR-129-5p could inhibit the degradation of IκBα and increase the apoptosis and reduce the migration of HCC cells by suppressing the expression of VCP. Our results revealed that the expression of VCP was directly regulated by miR-129-5p and this regulation played an important role in the progression of HCC.
    PLoS ONE 04/2012; 7(4):e35800. DOI:10.1371/journal.pone.0035800 · 3.53 Impact Factor
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    ABSTRACT: This work presents two methods, the Least-square and Bayesian method, to solve the multiple mapping problem in extracting gene expression profiles through the next-generation sequencing. We parallel the tag sequences to genome, and partition them to improving the methods’ efficiency. The essential feature of these methods is that they can solve the multiple mapping problem between genes and short-reads, while generating almost the same estimation in single-mapping situation as the traditional approaches. These two methods are compared by simulation and a real example, which was generated from radiation-induced lung cancer cells (A549), through mapping short-reads to human ncRNA database. The results show that the Bayesian method, as realized by Gibbs sampler, is more efficient and robust than the Least-square method.
    Frontiers of Mathematics in China 12/2011; 6(6). DOI:10.1007/s11464-011-0123-z · 0.45 Impact Factor
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    ABSTRACT: Most intronic micro-RNAs are coexpressed with their host genes, suggesting that they may play similar roles. The function of miR-483 remains unknown, although it is embedded in an intron of Igf2 gene, which is an activator of hepatocellular carcinoma proliferation. In the present study, we provide evidence that Igf2-derived miR-483 can induce proliferation in hepatocellular carcinoma cells. The miR-483 promotion of proliferation was analysed by soft agar colony formation assay and proliferation curve assay. The effect of miR-483 on Socs3 expression was examined by Western blot and a reporter assay. Our results revealed that Igf2-derived intronic miR-483 was identified by the application of 94G6, an inhibitor of Igf2 at the transcriptional level. All results from the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT assay, the proliferation curve assay and the soft agar colony formation assay showed that miR-483 promoted the proliferation of hepatocellular carcinoma cells. Finally, Socs3, a putative target predicted by bioinformatics, was regulated by miR-483 at mRNA and protein levels. Direct binding with the 3' UTR was identified by a luciferase activity assay. Our findings demonstrate that Igf2-derived intronic miR-483, through downregulation of its target Socs3, regulates hepatoma cell proliferation and thus may serve as a potential target for hepatocellular carcinoma therapy.
    Molecular and Cellular Biochemistry 11/2011; 361(1-2):337-43. DOI:10.1007/s11010-011-1121-x · 2.39 Impact Factor
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    ABSTRACT: Ionizing radiation (IR) causes severe cellular damage both directly and indirectly and disrupts RNA integrity. RNA strand breaks are the most frequent type of damage caused by IR. RNA damage is involved in the development of degenerative diseases, including Alzheimer’s disease and Parkinson’s disease. However, the mechanism of mRNA damage and any resulting pathophysiological outcomes are poorly understood. This is partly because there is a lack of sensitive tools to monitor damage randomly occurring in RNA, especially RNA strand break damage in a given RNA. In this work, a method using the reverse transcription polymerase chain reaction (RT-PCR) after poly(A) addition to 3′-end of RNA to determine RNA strand break damage in a specific RNA by poly(A) polymerase has been developed. The levels of damage in specific mRNAs, including ABL1, TP53, GADD45A and ATR from IR-treated HeLa cells were examined. Strand breaks were detected in all mRNAs examined. The study provides a novel and sensitive method based on 3′-end poly(A)-tailing RT-PCR to monitor RNA strand break damage. KeywordsRNA damage–RNA strand break–ionizing radiation–poly(A) polymerase–RT-PCR
    Chinese Science Bulletin 10/2011; 56(30):3172-3177. DOI:10.1007/s11434-011-4721-7 · 1.37 Impact Factor

Publication Stats

1k Citations
126.78 Total Impact Points

Institutions

  • 2014
    • Government of the People's Republic of China
      Peping, Beijing, China
  • 2009–2014
    • China Institute for Radiation Protection
      Peping, Beijing, China
  • 2012–2013
    • Academy of Military Medical Sciences
      T’ien-ching-shih, Tianjin Shi, China
  • 2011
    • Beijing FivePlus Molecular Medicine Institute
      Peping, Beijing, China
  • 2010
    • Beijing Proteome Research Center
      Peping, Beijing, China