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Tumour Biol. 2015 Nov 6. [Epub ahead of print]

miR-122 inhibits cancer cell malignancy by targeting PKM2 in gallbladder carcinoma.

Lu W1,2, Zhang Y1,3, Zhou L4, Wang X3, Mu J1, Jiang L1,3, Hu Y1,3, Dong P1, Liu Y5,6.

Author information

1
Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People's Republic of China.
2
Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China.
3
Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People's Republic of China.
4
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China.
5
Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People's Republic of China. liuybphd@126.com.
6
Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People's Republic of China. liuybphd@126.com.

Abstract

Gallbladder cancer (GBC) is one of the lethal diseases of digestive system. Increasing evidence prompt that microRNAs (miRs) might provide a novel therapeutical target for malignant disease. The antitumor effect of miR-122 to GBC is worth to be investigated. miR-122 expression level in GBC tissue sample and cell lines were assayed by qRT-PCR. miR-122 mimics were transfected for upregulation of miR-122 expression. Cell function was assayed by CCK8, flow cytometry, wound healing assay, migration assay, and invasion assay. The target genes of miR-122 were predicated by TargetScan online program and verified by western blot and luciferase report gene assay. miR-122 was decreased in GBC tissue and cell lines. The exogenous introduction of miR-122 exhibits multiple antitumor effect in GBC cell proliferation, invasion, and metastasis. Further studies revealed that the PKM2 was a regulative target of miR-122 in GBC cell. miR-122 also inhibits TGF-β-induced epithelium mesenchymal transformation of GBC cell by downregulating PKM2 expression. These findings suggest that miR-122 plays an important role in tumorigenesis of GBC through interfering PKM2, highlighting its usefulness as a potential therapeutic agent in GBC.

KEYWORDS:

Gallbladder carcinoma; Malignant; PKM2; miR-122

PMID:
26546436
DOI:
10.1007/s13277-015-4308-z

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