miR-21 promotes migration and invasion by the miR-21-PDCD4-AP-1 feedback             loop in human hepatocellular carcinoma.
Distant migration and invasion is the main contributor to the death of cancer             patients and miRNAs have been implicated in these processes. In the present study,             we identified the role of microRNA-21 (miR-21) in hepatocellular carcinoma (HCC)             migration and invasion and determined its underlying regulatory mechanism. miR-21             was significantly upregulated in HCC tissues and cell lines, compared with adjacent             non-tumor tissues and normal hepatic cells. miR-21 upregulation was associated             with the capacity of tumor migration and invasion in HCC. The expression level             of miR-21 was inversely correlated with the protein expression level of a previously             identified target gene, programmed cell death 4 (PDCD4). In HepG2 cells, inhibition             of miR-21 expression repressed cell migration and invasion by upregulating both             mRNA and protein levels of PDCD4 and downregulating key downstream signaling pathway             molecules, including phospho-c-Jun, matrix metalloproteinases (MMP)-2 and MMP-9.             Moreover, activation protein 1 (AP-1) could directly activate miR-21 transcription.             Taken together, these results provide evidence that miR-21 promotes migration             and invasion in HCC through the miR-21-PDCD4-AP-1 feedback loop, suggesting that             targeting the miR-21-PDCD4-AP-1 loop may represent a promising strategy in the             management of HCC.
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
Qin
Q
Zhu
Zhiming
Z
Wang
Yu
Y
Hu
Jindong
J
Li
Xinying
X
Li
Ledu
L
Zhou
Yun
Y
Huang
D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation
D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D018808:Transcription Factor AP-1