title: Long non-coding RNA URHC regulates cell proliferation and apoptosis via ZAK through the ERK/MAPK signaling pathway in hepatocellular carcinoma.
abstract: Long non-coding RNAs (lncRNAs) have previously been implicated in human disease states, especially cancer. Although the aberrant expression of lncRNAs has been observed in cancer, the biological functions and molecular mechanisms underlying aberrantly expressed lncRNAs in hepatocellular carcinoma (HCC) have not been widely established. In the present study, we investigated a novel lncRNA, termed URHC (up-regulated in hepatocellular carcinoma), and evaluated its role in the progression of HCC. Expression profiling using a lncRNA microarray revealed that URHC was highly expressed in 3 HCC cell lines compared to normal hepatocytes. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses confirmed that URHC expression was increased in hepatoma cells and HCC tissues. Moreover, using qRT-PCR, we confirmed that URHC expression was up-regulated in 30 HCC cases (57.7%) and that its higher expression was correlated with poor overall survival. We further demonstrated that URHC inhibition reduced cell proliferation and promoted apoptosis. We hypothesize that URHC may function by regulating the sterile alpha motif and leucine zipper containing kinase AZK (ZAK) gene, which is located near URHC on the same chromosome. We found that ZAK mRNA levels were down-regulated in HCC tissues and the expression levels of ZAK were negatively correlated with those of URHC in the above HCC tissues. Next, we confirmed that URHC down-regulated ZAK, which is involved in URHC-mediated cell proliferation and apoptosis. Furthermore, ERK/MAPK pathway inactivation partially accounted for URHC-ZAK-induced cell growth and apoptosis. Thus, we concluded that high URHC expression can promote cell proliferation and inhibit apoptosis by repressing ZAK expression through inactivation of the ERK/MAPK pathway. These findings may provide a novel mechanism and therapeutic targets for the treatment of HCC.
authors.affiliation: 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Xu
authors.affiliation: 2. Department of Occupational and Environmental Health, Faculty of Military Preventive Medicine, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Zhang
authors.affiliation: 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dang
authors.affiliation: 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Ti
authors.initials: T
authors.lastname: Zhou
authors.affiliation: 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Wang
authors.affiliation: 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Song
authors.affiliation: 1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Dou
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D020930:MAP Kinase Kinase Kinases; D020935:MAP Kinase Signaling System; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D062085:RNA, Long Noncoding; D011494:Protein Kinases; D020930:MAP Kinase Kinase Kinases; C413047:MAP3K20 protein, human
keywords: HCC; Long non-coding RNA; URHC; ZAK; apoptosis.; proliferation