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Run Zhai, Fang Tang, Jianhua Gong, Jing Zhang, Biao Lei, Bo Li, Yangchao Wei, Xingsi Liang, Bo Tang, Songqing He
Recent studies have shown that deubiquitination plays a key role in tumor progression, metastasis, resistance to chemotherapy drugs, and prognosis. In this study, we investigated the effects of the deubiquitinating enzyme USP22 on the expression of the drug-resistance genes BMI1 and EZH2 in hepatocellular carcinoma (HCC) and on prognosis. Downregulation of USP22 expression with interference ribonucleic acid in resistant HCC cell lines with high USP22 expression resulted in decreased BMI1 expression, but had no effect on EZH2 expression...
2016: OncoTargets and Therapy
Meng Zhou, Xiao-Yu Zhang, Xi Yu
BACKGROUND: Increasing evidences have demonstrated that the dysregulation of long non-coding RNAs (lncRNAs) may act as an important role in tumor progression. The long non-coding RNA SPRY4 intronic transcript 1 (SPRY4-IT1) has been reported in some cancer including regulating cell growth, differentiation, apoptosis, and cancer progression. However, the expression and function of SPRY4-IT1 in the progression of hepatocellular carcinoma (HCC) remain largely unknown. METHODS: The lncRNA SPRY4-IT1 was detected by quantitative real time PCR (qRT-PCR) in HCC cell lines, CCK8 cell proliferation and transwell invasion assays were performed to detect the GC cell proliferation and invasion abilities...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jun-Jie Zhang, Jiang-Tao Chen, Long Hua, Kun-Hou Yao, Chen-Yu Wang
Hepatocellular carcinoma (HCC) is a highly aggressive solid malignancy in the word. Aberrant microRNA (miRNA) expression is involved in human diseases including cancer. In the current study, we explore the function of miR-98 in HCC cell proliferation. We found that expression level of miR-98 was significantly decreased in HCC tissues and cells lines compared with adjacent non-tumor issues and human hepatic cell line LO2. Increased expression of miR-98 suppressed HCC cell proliferation and arrested HCC cell cycle in G0/G1 phase...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
N A Wijetunga, M Pascual, J Tozour, F Delahaye, M Alani, M Adeyeye, A W Wolkoff, A Verma, J M Greally
The predisposition of patients with Hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) involves components of viral infection, inflammation and time. The development of multifocal, genetically distinct tumours is suggestive of a field defect affecting the entire liver. The molecular susceptibility mediating such a field defect is not understood. One potential mediator of long-term cellular reprogramming is heritable (epigenetic) regulation of transcription, exemplified by DNA methylation. We studied epigenetic and transcriptional changes in HCV-infected livers in comparison with control, uninfected livers and HCC, allowing us to identify pre-neoplastic epigenetic and transcriptional events...
October 10, 2016: Oncogene
Yun Huang, Yiming Tao, Kuan Hu, Feng Lin, Xinying Li, Tiecheng Feng, Zhi-Ming Wang
Hypoxia is known to promote hepatocellular carcinoma (HCC) invasion and metastasis and nuclear inhibitor of protein phosphatase 1 (NIPP1) overexpression contributes to the malignant phenotype in HCC. The aim of this study was to investigate the role of NIPP1 in HCC development under hypoxia. We first conducted a study with 106 cases to explore the association of NIPP1 and/or enhancer of zeste homolog 2 (EZH2) expression with poor prognosis in HCC. Then additional 352 independent cases were recruited to validate the results in the first stage...
November 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jing Fang, Cheng-Cao Sun, Cheng Gong
Recently, long noncoding RNAs (lncRNAs) have been identified as critical regulators in numerous types of cancers, including non-small cell lung cancer (NSCLC). X inactivate-specific transcript (XIST) has been found to be up-regulated and acts as an oncogene in gastric cancer and hepatocellular carcinoma, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Here, we identified XIST as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found that XIST is over-expressed in NSCLC, and its increased level is associated with shorter survival and poorer prognosis...
September 16, 2016: Biochemical and Biophysical Research Communications
Xiao-Jun Yang, Chao-Qun Huang, Chun-Wei Peng, Jin-Xuan Hou, Jiu-Yang Liu
Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival...
October 30, 2016: Gene
Cheng-Jun Sui, Yan-Ming Zhou, Wei-Feng Shen, Bing-Hua Dai, Jiong-Jiong Lu, Min-Feng Zhang, Jia-Mei Yang
: Long noncoding RNAs (lncRNAs) have been reported to play pivotal roles in a variety of cancers. However, lncRNAs involved in hepatocellular carcinoma (HCC) initiation and progression remain largely unclear. In this study, we identified an lncRNA gradually increased during hepatocarcinogenesis (lncRNA-GIHCG) using publicly available microarray data. Our results further revealed that GIHCG is upregulated in HCC tissues in comparison with adjacent non-tumor tissues. High GIHCG expression is correlated with large tumor size, microvascular invasion, advanced BCLC stage, and poor survival of HCC patients...
July 5, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Fengqi Nie, Xiang Yu, Mingde Huang, Yunfei Wang, Min Xie, Hongwei Ma, Zhaoxia Wang, Wei De, Ming Sun
Recently, long noncoding RNAs have been emerged as critical regulators of human disease and prognostic markers in several cancers, including gastric cancer. In this study, we globally assessed the transcriptomic differences of lncRNAs in gastric cancer using publicly available microarray data from Gene Expression Omnibus (GEO) and identified an oncogenetic lncRNA ZFAS1, which may promote gastric tumorigenesis. ZFAS1 has been found to be upregulated and function as oncogene in colorectal cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in gastric cancer is still undetermined...
May 26, 2016: Oncotarget
Pingping Zhu, Yanying Wang, Guanling Huang, Buqing Ye, Benyu Liu, Jiayi Wu, Ying Du, Lei He, Zusen Fan
Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC); however, the molecular mechanisms underlying their self-renewal and differentiation remain largely unknown. Through analysis of transcriptome microarray data, we identified a long noncoding RNA (lncRNA) called lnc-β-Catm, which is highly expressed in human HCC tumors and liver CSCs. We found that lnc-β-Catm is required for self-renewal of liver CSCs and tumor propagation in mice...
July 2016: Nature Structural & Molecular Biology
Jie Li, Sheng Zhang, Qing Hu, Kang Zhang, Jianbin Jin, Xuqing Zheng, Zhenyu Yin, Xiaomin Wang
Hepatocellular carcinoma (HCC) is complicated by aggressive migration and invasion, which contribute to the increased mortality of HCC patients. The NKD1 protein is abnormally expressed in many neoplasms and plays an important role in tumor progression. However, the regulation and underlying molecular mechanisms of NKD1 in HCC cell invasion and migration remain poorly understood. In the present study, ectopic expression of NKD1 in HCC cells attenuated migration and invasion in vitro and in vivo by down-regulating Rac1 expression level and activity, which affected the HCC cell cytoskeleton and E-cadherin expression...
2016: Scientific Reports
Chang-Peng Li, Mu-Yan Cai, Li-Juan Jiang, Shi-Juan Mai, Jie-Wei Chen, Feng-Wei Wang, Yi-Ji Liao, Wen-Hui Chen, Xiao-Han Jin, Xiao-Qing Pei, Xin-Yuan Guan, Mu-Sheng Zeng, Dan Xie
Trimethylation of lysine 27 on histone H3 (H3K27ME3) is a transcription-suppressive histone mark mediated by enhancer of zeste homolog 2 (EZH2). We have previously suggested that EZH2-mediated H3K27ME3 plays a critical oncogenic role in human hepatocellular carcinoma (HCC) aggressiveness. However, the direct downstream targets of EZH2-H3K27ME3 and the molecular mechanisms by which regulates HCC pathogenesis remain unclear. In this study, we used chromatin immunoprecipitation together with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis to assess genome-wide chromatin occupancy of H3K27ME3 in HCC cells...
2016: Carcinogenesis
Jiao-Jiao Hu, Wei Song, Shao-Dan Zhang, Xiao-Hui Shen, Xue-Mei Qiu, Hua-Zhang Wu, Pi-Hai Gong, Sen Lu, Zhu-Jiang Zhao, Ming-Liang He, Hong Fan
It is well accepted that HBx plays the major role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. However, little was known about its role in regulating long noncoding RNAs (lncRNAs), a large group of transcripts regulating a variety of biological processes including carcinogenesis in mammalian cells. Here we report that HBx upregulates UCA1 genes and downregulates p27 genes in hepatic LO2 cells. Further studies show that the upregulated UCA1 promotes cell growth by facilitating G1/S transition through CDK2 in both hepatic and hepatoma cells...
March 24, 2016: Scientific Reports
Han Han, Wenjuan Li, Hongxing Shen, Jinxiang Zhang, Yahui Zhu, Youjun Li
Deregulation of microRNAs (miRNAs) and c-Myc (Myc) contributes to hepatocellular carcinoma (HCC) progression, but how miRNAs and Myc regulate each other in hepatocarcinogenesis is still poorly understood. Using a functional screen, we identified miR-129-5p as a miRNA that inhibits HCC cell growth. miR-129-5p targets the mitochondrial matrix protein pyruvate dehydrogenase kinase 4 (PDK4), which leads to decreased phosphorylation of the E1α subunit of pyruvate dehyrogenase (PDH) complex, inhibition of glycolysis, retarded tumor growth, and impaired lung colonization...
March 21, 2016: Journal of Molecular Cell Biology
Tsang-Pai Liu, Yi-Han Hong, Kwang-Yi Tung, Pei-Ming Yang
There are currently no effective molecular targeted therapies for hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 (H3K27)-specific methyltransferase, has been emerged as novel anticancer target. Our previous study has demonstrated that GSK343, an S-adenosyl-L-methionine (SAM)-competitive inhibitor of EZH2, induces autophagy and enhances drug sensitivity in cancer cells including HCC. In this study, an in silico study was performed and found that EZH2 was overexpressed in cancerous tissues of HCC patients at both gene and protein levels...
2016: Oncoscience
Daisy P F Tsang, William K K Wu, Wei Kang, Ying-Ying Lee, Feng Wu, Zhuo Yu, Lei Xiong, Anthony W Chan, Joanna H Tong, Weiqin Yang, May S M Li, Suki S Lau, Xiangchun Li, Sau-Dan Lee, Yihua Yang, Paul B S Lai, Dae-Yeul Yu, Gang Xu, Kwok-Wai Lo, Matthew T V Chan, Huating Wang, Tin L Lee, Jun Yu, Nathalie Wong, Kevin Y Yip, Ka-Fai To, Alfred S L Cheng
Enhancer of zeste homolog 2 (EZH2) catalyses histone H3 lysine 27 trimethylation (H3K27me3) to silence tumour-suppressor genes in hepatocellular carcinoma (HCC) but the process of locus-specific recruitment remains elusive. Here we investigated the transcription factors involved and the molecular consequences in HCC development. The genome-wide distribution of H3K27me3 was determined by chromatin immunoprecipitation coupled with high-throughput sequencing or promoter array analyses in HCC cells from hepatitis B virus (HBV) X protein transgenic mouse and human cell models...
April 2016: Journal of Pathology
Chunbo Zhuang, Pei Wang, Da Huang, Luming Xu, Xiaobei Wang, Lin Wang, Lihua Hu
Accumulating evidence demonstrates the important roles of microRNAs (miRNAs) in tumor development and progression. miR-26a has been reported to be downregulated in several types of cancers including hepatocellular carcinoma, but the underlying mechanism of how miR-26a is repressed remains largely unknown. In the present study, we performed western blot analysis, qRT-PCR, luciferase reporter assay and chromatin immunoprecipitation assay to investigate the relationship between miR-26a and the enhancer of zest homologue 2 (EZH2)...
March 2016: International Journal of Oncology
Fang Yang, Li-Zhi Lv, Qiu-Cheng Cai, Yi Jiang
AIM: To investigate the potential roles of enhancer of zeste homolog2 (EZH2), Bmi-1 and miR-203 in cell proliferation and invasion in hepatocellular carcinoma (HCC) cell line Hep3B. METHODS: A total of 73 patients who underwent surgical resection at Fuzong Clinical Medical College of Fujian Medical University were enrolled in this study. Hep3B cells were cultivated in RPMI 1640 medium supplemented with 10% fetal bovine serum at 37 °C. Vectors that containing cDNA of the EZH2 gene or miR-203 targeted shRNA plasmid were constructed, and then transfected into Hep3B cells...
December 21, 2015: World Journal of Gastroenterology: WJG
Shu-Bin Gao, Shi-Long Sun, Qi-Lin Zheng, Li Zhang, Yuequan Zhu, Guang-Hui Jin, Li-Xiang Xue
Although the abnormal expression of Polycomb-group (PcG) proteins is closely associated with carcinogenesis and the clinicopathological features of hepatocellular carcinoma (HCC), the genetic mutation profile of PcG genes has not been well established. In this study of human HCC specimens, we firstly discovered a highly conserved mutation site, G553C, in the Polycomb Repressive Complex 2 (PRC2) gene enhancer of zeste homolog 2 (EZH2). This site also harbors a single nucleotide polymorphism (SNP), rs2302427, which plays an important antagonistic role in HCC...
2015: American Journal of Cancer Research
Cheng-Rong Xie, Zhao Li, Hong-Guang Sun, Fu-Qiang Wang, Yu Sun, Wen-Xiu Zhao, Sheng Zhang, Wen-Xing Zhao, Xiao-Min Wang, Zhen-Yu Yin
Chromodomain helicase DNA binding protein 5 (CHD5) acts as a tumor suppressor in many cancers. In the present study, we demonstrated that reduced levels of CHD5 in hepatocellular carcinoma (HCC) tissues were significantly associated with metastasis and poor prognosis. Gain-of-function assays revealed that CHD5 suppressed motility and invasion of HCC cells. Subsequent investigations showed that CHD5 was epigenetically silenced by polycomb repressive complex 2 (PRC2)-mediated the trimethylation of histone H3 at lysine 27 (H3K27me3) in HCC cells...
December 1, 2015: Oncotarget
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