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HCC and p21

Luca Tordella, Sadaf Khan, Anja Hohmeyer, Ana Banito, Sabrina Klotz, Selina Raguz, Nadine Martin, Gopuraja Dhamarlingam, Thomas Carroll, José Mario González Meljem, Sumit Deswal, Juan Pedro Martínez-Barbera, Ramón García-Escudero, Johannes Zuber, Lars Zender, Jesús Gil
Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumors. ARID1B controls p16(INK4a) and p21(CIP1a) transcription but also regulates DNA damage, oxidative stress, and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence...
October 13, 2016: Genes & Development
Jian Ye, Yufeng Yao, Qixue Song, Sisi Li, Zhenkun Hu, Yubing Yu, Changqing Hu, Xingwen Da, Hui Li, Qiuyun Chen, Qing K Wang
Hepatocellular carcinoma (HCC) is one of the most common malignant cancers. To elucidate new regulatory mechanisms for heptocarcinogenesis, we investigated the regulation of p21, a cyclin-dependent kinase (CDK) inhibitor encoded by CDKN1A, in HCC. The expression level of p21 is decreased with the progression of HCC. Luciferase assays with a luciferase-p21-3' UTR reporter and its serial deletions identified a 15-bp repressor element at the 3'-UTR of CDKN1A, which contains a binding site for miR-95-3p. Mutation of the binding site eliminated the regulatory effect of miR-95-3p on p21 expression...
October 4, 2016: Scientific Reports
Dongzhi Wang, Renan Chang, Gang Wang, Baoying Hu, Yong Qiang, Zhong Chen
BACKGROUND: Recent investigations have implicated that Chitosan-nucleotide nanoparticles might be useful non-viral carriers in gene therapy. Polo-like kinase 1 (PLK1) has been reported to be an important oncogene that exerted considerable therapeutic value in hepatocellular carcinoma (HCC). OBJECTIVE: We explored whether Galactosylated chitosan-graft-poly(ethylene glycol) (GCP) nanoparticle-mediated delivery of PLK1 siRNA nucleotides could serve as an effective anti-cancer agent for HCC therapy...
September 26, 2016: Anti-cancer Agents in Medicinal Chemistry
Jae Woo Jung, So-Mi Yoon, Subin Kim, Yun-Hui Jeon, Byung-Hak Yoon, Su-Geun Yang, Min Kyoung Kim, Senyon Choe, Mario Meng-Chiang Kuo
The biological role of BMP-9 signaling in liver cancer remains dubious. To explore the potential use of BMP-9 signaling for anti-cancer therapy, we used recombinant human BMP-9, which we referred to as MB109, to study the effect on growth of fifteen hepatocellular carcinoma (HCC) cell lines. MB109 effectively inhibits the proliferation of nine HCC cells in vitro. The anti-proliferative effect was found to be induced by turning on p21 signaling, which caused survivin suppression and G0/G1 cell cycle arrest. ID3 was identified to be the mediator of the MB109-induced p21 expression...
September 16, 2016: Oncotarget
Masayoshi Yamaguchi, Satoru Osuka, M Neale Weitzmann, Bassel F El-Rayes, Mamoru Shoji, Tomiyasu Murata
Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and ranks third in overall global cancer-related mortality rates. Importantly, in this study gene expression data demonstrate that prolonged survival in HCC patients is associated with increased regucalcin gene expression. Regucalcin has been shown to play a pivotal role as a transcription repressor and diminished expression or activity of regucalcin may play a key role in the development of human carcinogenesis. Indeed, overexpression of regucalcin suppressed the proliferation, cell death, and migration of human HCC HepG2 cells in vitro...
October 2016: International Journal of Oncology
Danyang Liu, Yonglong Zhang, Yingze Wei, Guoyuan Liu, Yufeng Liu, Qiongmei Gao, Liping Zou, Wenjiao Zeng, Nong Zhang
Nuclear factor erythroid-2-related factor 2 (Nrf2), a master transcription factor in the antioxidant response, has been found to be ubiquitously expressed in various cancer cells and in the regulation tumor proliferation, invasion, and chemoresistance activities. The regulatory roles of Nrf2 in controlling Hepatocellular carcinoma (HCC) progression remain unclear. In this study, we demonstrated that Nrf2 was significantly elevated in HCC cells and tissues and was correlated with poor prognosis of HCCs. Consistently, Nrf2 significantly promoted HCC cell growth both in vitro and in vivo...
August 30, 2016: Oncotarget
Yue-Yuan Lai, Fei Shen, Wen-Song Cai, Ji-Wei Chen, Jian-Hua Feng, Jie Cao, Huan-Qing Xiao, Guang-Hui Zhu, Bo Xu
Acquired evidence indicated that microRNAs (miRNAs) played essential roles in cancer development, including hepatocellular carcinoma (HCC). Functions and mechanisms of miRNAs involved in HCC remain largely unknown. Here, we found that miR-384 was significantly downregulated in HCC cells and tissues by RT-PCR. Gain and loss of function studies revealed that miR-384 significantly suppressed HCC cell proliferation. Insulin receptor substrate 1(IRS1) was identified as a direct and functional target of miR-384. Moreover, miR-384 decreased IRS1 expression, subsequently downregulating cyclin D1 and upregulating p21 and p-Rb expression...
August 19, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Lili Cao, Lijun Zhang, Xiang Zhao, Ye Zhang
Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3',4',5'-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC...
2016: PloS One
Chuangye Han, Xiwen Liao, Wei Qin, Long Yu, Xiaoguang Liu, Gang Chen, Zhengtao Liu, Sicong Lu, Zhiwei Chen, Hao Su, Guangzhi Zhu, Zili Lu, Zhiming Liu, Xue Qin, Ying Gui, Zengnan Mo, Lequn Li, Tao Peng
This study was to explore the association between gene variants and p21 expression and investigate the TP53-independent p21 regulation in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients from Guangxi by genome-wide association study. 426 HBV-related HCC patients were enrolled. Results showed that, after quality control, a total of 21,643 SNPs were identified in 107 p21 positive and 298 p21 negative patients. The variants of epidermal growth factor receptor (EGFR; rs2227983 and rs6950826) and spectrin repeat containing, nuclear envelope 2 (SYNE2; rs8010699, rs4027405 and rs1890908) were associated with p21 expression...
2016: Scientific Reports
Joan J Castellano, Alfons Navarro, Nuria Viñolas, Ramon M Marrades, Jorge Moises, Anna Cordeiro, Adela Saco, Carmen Muñoz, Dolors Fuster, Laureano Molins, Josep Ramirez, Mariano Monzo
INTRODUCTION: Long intergenic noncoding RNA-p21 (lincRNA-p21) is a long noncoding RNA transcriptionally activated by tumor protein p53 (TP53) and hypoxia inducible factor 1 alpha subunit (HIF1A). It is involved in the regulation of TP53-dependent apoptosis and the Warburg effect. We have investigated the role of lincRNA-p21 in NSCLC. METHODS: LincRNA-p21 expression was assessed in tumor and normal tissue from 128 patients with NSCLC and correlated with time to relapse and cancer-specific survival (CSS)...
August 2, 2016: Journal of Thoracic Oncology
Sidra Majaz, Zhangwei Tong, Kesong Peng, Wei Wang, Wenjing Ren, Ming Li, Kun Liu, Pingli Mo, Wengang Li, Chundong Yu
BACKGROUND: General control non-depressible 5 (GCN5) is a crucial catalytic component of a transcriptional regulatory complex that plays important roles in cellular functions from cell cycle regulation to DNA damage repair. Although GCN5 has recently been implicated in certain oncogenic roles, its role in liver cancer progression remains vague. RESULTS: In this study, we report that GCN5 was overexpressed in 17 (54.8 %) of 31 human hepatocellular carcinoma (HCC) specimens...
2016: Cell & Bioscience
Nargis Rakshit, Sijun Yang, Wei Zhou, Yi Xu, Chenghui Deng, Jiecheng Yang, Huijun Yu, Wenxiang Wei
Both inhibitor of growth 4 (ING4) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) are well known as tumor suppressors that are closely related to tumor occurrence and progression. It was reported that ING4 and PTEN showed synergistic antitumor activities in nasopharyngeal carcinoma cells. The two tumor suppressors demonstrated synergistic effect on growth inhibition and apoptosis activation. In this study, we investigated their therapeutic potential in hepatocellular carcinoma (HCC) cells...
August 2016: Acta Biochimica et Biophysica Sinica
Meng Jia, Li Jiang, Ya-Dong Wang, Jin-Zhao Huang, Miao Yu, Huan-Zhou Xue
AIM: Emerging evidence has showed that long non-coding RNA (lncRNA) play an important role in the occurrence and development of various cancers. In the present study, the expression level of lincRNA-p21 was investigated in hepatocellular carcinoma (HCC), and its role in invasion of HCC was also explored. METHODS: The lincRNA-p21 levels in human HCC tumor tissue and cell lines HepG2 and SMMC-7721 were determined by real-time polymerase chain reaction. Transfected HCC cells with pcDNA-lincRNA-p21 or si-lincRNA-p21 for overexpression or downregulation of lincRNA-p21, the Notch signaling and epithelial-mesenchymal transition (EMT)-related proteins and cell invasion were measured by western blot and Transwell assay, respectively...
February 1, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Hui Liu, Feihu Chen, Ling Zhang, Qing Zhou, Shuyu Gui, Yuan Wang
4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative, was reported to function as a tumor inhibitor in various types of cancer cells in vitro. However, little is known concerning its antitumor effect on human hepatocellular carcinoma (HCC) HepG2 cells. The aims of the present study were to investigate the effects of ATPR on the proliferation of HepG2 cells and to explore the probable mechanisms. A series of experiments were performed following the treatment of HepG2 cells with ATRA and ATPR...
July 2016: Oncology Reports
Changwen Bo, Na Li, Xiuli Li, Xianwei Liang, Yonghui An
Hepatocellular carcinoma (HCC) is one of the most common human cancers all over the world. Increasing evidences have demonstrated that long noncoding RNAs (lncRNAs) play important roles in malignant transformation, tumor growth and metastasis in HCC. Among lncRNAs, ultraconserved RNAs (ucRNAs) containing an ultraconserved region have been report to contribute to human cancers. lncRNA ultraconserved element 338 (uc.338) was first found to be upregulated in HCC and promote cell growth. However, the exact mechanism by which uc...
October 2016: Human Cell
Sahar Olsadat Sajadian, Chaturvedula Tripura, Fazel Sahraneshin Samani, Marc Ruoss, Steven Dooley, Hossein Baharvand, Andreas K Nussler
BACKGROUND: 5-Azacytidine (5-AZA), a DNA methyl transferase inhibitor, is a clinically used epigenetic drug for cancer therapy. Recently, we have shown that 5-AZA upregulates ten-eleven translocation (TET) protein expression in hepatocellular carcinoma (HCC) cells, which induce active demethylation. Vitamin C facilitates TET activity and enhances active demethylation. The aim of this study is to investigate whether vitamin C is able to enhance the effect of 5-AZA on active demethylation and to evaluate its consequence in HCC cell lines...
2016: Clinical Epigenetics
Hong-Hao Zhou, Lin Chen, Hui-Fang Liang, Guang-Zhen Li, Bi-Xiang Zhang, Xiao-Ping Chen
BACKGROUND: Heptocelluar carcinoma (HCC) is insensitive to chemotherapy due to limited bioavailability and acquired drug resistance. Smad3 plays dual roles by inhibiting cell growth initially and promoting the progression of advanced tumors in HCC. However, the role of smad3 in chemosensitivity of HCC remains elusive. METHODS: The role of smad3 in chemosensitivity of HCC was measured by cell viability, apoptosis, plate colony formation assays and xenograft tumor models...
2016: International Journal of Molecular Sciences
Bin-Hui Xie, Xiao He, Rui-Xi Hua, Bing Zhang, Guo-Sheng Tan, Shi-Qiu Xiong, Liang-Shuai Liu, Wei Chen, Jian-Yong Yang, Xiao-Nong Wang, He-Ping Li
microRNAs (miRNAs) dysregulation is widely involved in cancer progression and contributed to sustained cell proliferation by directly targeting multiple targets. Therefore, better understanding the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In our study, we found that mir-765 is upregulated in both hepatocellular carcinoma (HCC) cell lines and tissues, compared to human normal liver cell line and adjacent non-cancerous tissues, respectively...
2016: Cancer Biomarkers: Section A of Disease Markers
Guizhou Zhu, Tao Tao, Dongmei Zhang, Xiaojuan Liu, Huiyuan Qiu, LiJian Han, Zhiwei Xu, Ying Xiao, Chun Cheng, Aiguo Shen
Hepatocellular carcinoma (HCC) is a malignant tumor originating in the liver. Previous studies have indicated that O-GlcNAc transferase (OGT) and histone deacetylase-1 (HDAC1) play important roles in the pathogenesis of HCC. In the present study, we investigated the physical link between OGT and HDAC1. The O-GlcNAcylation of HDAC1 is overexpressed in HCC. We found that HDAC1 has two major sites of O-GlcNAcylation in its histone deacetylase domain. HDAC1 O-GlcNAcylation increases the activated phosphorylation of HDAC1, which enhances its enzyme activity...
August 2016: Glycobiology
A C Mamede, S Guerra, M Laranjo, K Santos, M J Carvalho, T Carvalheiro, P Moura, A Paiva, A M Abrantes, C J Maia, M F Botelho
The anticancer effects of human amniotic membrane (hAM) have been studied over the last decade. However, the action mechanisms responsible for these effects are not fully understood until now. Previously results reported by our team proved that hAM is able to induce cytotoxicity and cell death in hepatocellular carcinoma (HCC), a worldwide high incident and mortal cancer. Therefore, this experimental study aimed to investigate the cellular targets of hAM protein extracts (hAMPE) in HCC through in vitro studies...
October 2016: Pathology Oncology Research: POR
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