title: Identification of long noncoding RNA expression profile in oxaliplatin-resistant hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) is the most prevalent and malignant type of liver cancer. Besides the high incidence, the resistance to chemotherapy is a major problem that leads to the high mortality of HCC. Recently, aberrant expression of long noncoding RNAs (lncRNAs) has been considered as a primary feature of many types of cancer. However, the genome-wide expression pattern and associated functional implications of lncRNAs in chemo-resistant HCC cells remain unknown. In this study, we identified 120 differentially expressed lncRNAs with 61 up-regulated and 59 down-regulated (fold change>2, p<0.05) along with 421 differentially expressed mRNAs with 228 up-regulated and 193 down-regulated (fold change>2, p<0.05) in oxaliplatin-resistant (MHCC97H-OXA) HCC cells, compared to parental oxaliplatin-sensitive (MHCC97H) by microarray. The underlying pathways were related to cell death, proliferation, cellular response to stimulus, including p53 pathway, ErbB pathway and MAPK pathway. Further, 16 lncRNAs were selected for validation of microarray results with quantitative PCR, and a strong correlation was identified between the qPCR results and microarray data. We demonstrated for the first time that ENST00000438347, NR_073453 and ENST00000502804 were up-regulated in MHCC97H-OXA cells as well as chemo-resistant HCC cancerous tissues. Moreover, the expression of ENST00000518376 was significantly associated with the tumor size and differentiation. Overall survival analysis showed that high expression of ENST00000438347 and ENST00000518376 was associated with poor prognosis in HCC patients. Taken together, our results reveal that the expression profile in oxaliplatin-resistant HCC is significantly altered including lncRNAs. And a series of de novo lncRNAs play important functions in HCC oxaliplatin resistance and HCC progression.
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: yin.xin@zs-hospital.sh.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Yin
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: 339444217@qq.com.
authors.forename: Su-Su
authors.initials: SS
authors.lastname: Zheng
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: zhang.lan@zs-hospital.sh.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: xie.xiaoying@zs-hospital.sh.cn.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Xie
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: wang.yan@zs-hospital.sh.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: zhang.boheng@zs-hospital.sh.cn.
authors.forename: Bo-Heng
authors.initials: BH
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: wu.weizhong@zs-hospital.sh.cn.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Wu
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: qiu.shuangjian@zs-hospital.sh.cn.
authors.forename: Shuangjian
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: Ren.zhenggang@zs-hospital.sh.cn.
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Ren
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D063990:Gene Ontology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D000077150:Oxaliplatin
keywords: Hepatocellular carcinoma; Microarray; Oxaliplatin-resistant; Prognosis; lncRNA