title: miR-125/Pokemon auto-circuit contributes to the progression of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a type of human malignant tumor occurring in hepatic tissues with high mortality. Patients benefit little from current therapeutic modalities, at least partially due to the lack of complete elucidation of molecular network regulating HCC. miR-125 and Pokemon are well-recognized tumor suppressor and oncogenes for HCC, respectively. However, the underlying mechanism by which the two genes exert their functions and the relationship between miR-125 and Pokemon is still unexplored yet. In this study, we found that there is an inverse association between miR-125 and Pokemon expression levels in HCC specimen and cell lines. Online database mining indicated that there are three putative mRNA recognition elements (MREs) of miR-125 within 3' untranslated region (3'UTR) of Pokemon. MREs of miR-125 confer the expression of luciferase with a miR-125-dependent fashion. The alteration in miR-125 abundance regulates the expression of Pokemon at both protein and mRNA levels. Overexpression of Pokemon is able to abrogate the inhibitory effect of miR-125 on HCC progression. Further study showed that Pokemon inhibits the expression of miR-125 by binding of recognition sites within its promoter. In conclusion, we found that there is an auto-regulatory circuit consisting of miR-125 and Pokemon, which promotes the progression of HCC and may be a promising therapeutic target in clinical HCC treatment.
authors.affiliation: Faculty of Life Science and Chemical Engineering, Huaiyin Institute of Technology, 1 Meicheng Road East, Huai'an, 223003, Jiangsu, People's Republic of China. cpukj@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Kong
authors.affiliation: Faculty of Life Science and Chemical Engineering, Huaiyin Institute of Technology, 1 Meicheng Road East, Huai'an, 223003, Jiangsu, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Faculty of Life Science and Chemical Engineering, Huaiyin Institute of Technology, 1 Meicheng Road East, Huai'an, 223003, Jiangsu, People's Republic of China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, People's Republic of China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao, 266071, Shandong, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Faculty of Life Science and Chemical Engineering, Huaiyin Institute of Technology, 1 Meicheng Road East, Huai'an, 223003, Jiangsu, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Faculty of Life Science and Chemical Engineering, Huaiyin Institute of Technology, 1 Meicheng Road East, Huai'an, 223003, Jiangsu, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors; C485514:ZBTB7A protein, human
keywords: HCC; Pokemon; miR-125