title: Overexpression of Long Non-Coding RNA MEG3 Inhibits Proliferation of Hepatocellular Carcinoma Huh7 Cells via Negative Modulation of miRNA-664.
abstract: Evidence is accumulating that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis and dysregulated in many cancers, including hepatocellular carcinoma (HCC). Because lncRNAs can regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, lncRNAs are valuable biomarkers and therapeutic targets. Maternally expressed gene 3 (MEG3) is a lncRNA overexpressed in HCC cells that inhibits HCC progression, however, the mechanism remains largely unknown. Recently, a novel regulatory mechanism has been proposed in which RNAs can cross-talk with each other via competing for shared microRNAs (miRNAs). The proposed competitive endogenous RNAs could mediate the bioavailability of miRNAs on their targets, thus imposing another level of post-transcriptional regulation. In the current study, we demonstrated that MEG3 is down-regulated in HCC tissues. MEG3 over-expression imposes another level of post-transcriptional regulation, whereas MEG3 overexpression increase the expression of the miR-664 target gene, ADH4, through competitive "sponging" miR-664. In addition, NF-κB may affect transcription of MEG3 by directly binding to the promoter region. Our data revealed that NF-κB may affect the transcript of MEG3. MEG3 overexpression inhibited the proliferation of HCC cells, at least in part by affecting miR-664mediated regulation of ADH4. Together, these results suggest that MEG3 is a suppressor of tumor which acts in part through "sponging" miR-664. J. Cell. Biochem. 118: 3713-3721, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Laboratory, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, China.
authors.forename: Jin-Hua
authors.identifier: 0000-0002-6302-0530
authors.initials: JH
authors.lastname: He
authors.affiliation: Department of Laboratory, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, China.
authors.forename: Ze-Ping
authors.initials: ZP
authors.lastname: Han
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Liu
authors.affiliation: Department of Laboratory, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, China.
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Zhou
authors.affiliation: Department of Laboratory, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, China.
authors.forename: Mao-Xian
authors.initials: MX
authors.lastname: Zou
authors.affiliation: Department of Laboratory, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, China.
authors.forename: Yu-Bing
authors.initials: YB
authors.lastname: Lv
authors.affiliation: Department of Laboratory, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, China.
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Li
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Cao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C498907:MEG3 non-coding RNA, human; C000590115:MIRN664 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm
keywords: ALCOHOL DEHYDROGENASE 4; HEPATOCELLULAR CARCINOMA; LONG NON-CODING RNA; MATERNALLY EXPRESSED GENE 3; MICRORNA-664