PIK3C2A mRNA functions as a miR-124 sponge to facilitate CD151 expression and enhance malignancy of hepatocellular carcinoma cells.
Competing endogenous RNAs (ceRNAs) are RNA transcripts that can crosstalk with each other by competing for shared microRNAs (miRNAs) through miRNA response elements (MREs). Involved in ceRNA networks, the RNA transcripts may be in a balance, disruption of which could lead to tumorigenesis. Here we reveal a ceRNA interaction between PIK3C2A and CD151 mRNAs in hepatocellular carcinoma (HCC) cells. PIK3C2A is a candidate ceRNA of CD151 because mRNA 3' untranslated regions (3'UTRs) of these two genes contain miR-124 binding sites. miR-124 is downregulated, while PIK3C2A and CD151 are upregulated in HCC cells compared with normal hepatocytes. Direct and negative regulation of PIK3C2A and CD151 by miR-124 was confirmed in HCC cells. miR-124 and the two potential ceRNAs are all recruited to the RNA-induced silencing complex (RISC). In HCC cell lines QGY- 7703 and SMMC-7721, and normal hepatic cell line HL-7702, miR-124 plays a tumor suppressor role by targeting PIK3C2A and CD151. The MREs within PIK3C2A 3'UTR can independently stimulate CD151 expression level by acting as miR-124 decoys. PIK3C2A MREs enhance HCC cell malignancy by absorbing endogenous miR-124 and activating CD151 in HCC cells. We conclude that PIK3C2A 3'UTR functions as a trans activator to stimulate CD151 by competing for miR-124 binding in HCC cells. The collaboration of PIK3C2A and CD151 through ceRNA mechanism may be implicated in HCC initiation and development.
Key Laboratory for Critical Care Medicine of The Ministry of Health, Tianjin First Central Hospital, Tianjin, China.|Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.
Tao
T
Liu
First Center Clinical College, Tianjin Medical University, Tianjin, China.
Cai-Hua
CH
Zu
Key Laboratory for Critical Care Medicine of The Ministry of Health, Tianjin First Central Hospital, Tianjin, China.|Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.
Shu-Sen
SS
Wang
Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.
Hong-Li
HL
Song
Department of Pathology, Tianjin First Central Hospital, Tianjin, China.|Biobank of Tianjin First Central Hospital, Tianjin, China.
Zheng-Lu
ZL
Wang
Key Laboratory for Critical Care Medicine of The Ministry of Health, Tianjin First Central Hospital, Tianjin, China.
Xin-Nv
XN
Xu
Key Laboratory for Critical Care Medicine of The Ministry of Health, Tianjin First Central Hospital, Tianjin, China.
Hong-Sheng
HS
Liu
Key Laboratory for Critical Care Medicine of The Ministry of Health, Tianjin First Central Hospital, Tianjin, China.|Clinical Laboratory, Tianjin First Central Hospital, Tianjin, China.
Yu-Liang
YL
Wang
Key Laboratory for Critical Care Medicine of The Ministry of Health, Tianjin First Central Hospital, Tianjin, China.|Organ Transplant Center, Tianjin First Central Hospital, Tianjin, China.
Zhong-Yang
ZY
Shen
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D022781:Hepatocytes; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D060185:Tetraspanin 24 / Q000378:metabolism*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D020413:3' Untranslated Regions; C554715:CD151 protein, human; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex; D060185:Tetraspanin 24; D019869:Phosphatidylinositol 3-Kinases; C546621:PIK3C2A protein, human
CD151; PIK3C2A; competing endogenous RNA; hepatocellular carcinoma; microRNA