Long non-coding RNA LINC00152 promotes gallbladder cancer metastasis and epithelial–mesenchymal transition by regulating HIF-1α via miR-138

Author:

Cai Qiang1,Wang Zhenqiang2,Wang Shouhua1,Weng Mingzhe1,Zhou Di1,Li Chen2,Wang Jiandong1,Chen Erzhen3,Quan Zhiwei1ORCID

Affiliation:

1. Department of General Surgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200092, People's Republic of China

2. Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, People's Republic of China

3. Department of Emergency, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, People's Republic of China

Abstract

Long non-coding RNA LINC00152 had been reported as an oncogene in gastric and hepatocellular cancer. In this study, we show that LINC00152 is overexpressed in gallbladder cancer (GBC) tissue samples and cell lines. The high LINC00152 levels correlated negatively with the overall survival time in GBC patients. Functionally, LINC00152 dramatically promoted cell migration, invasion and epithelial–mesenchymal transition (EMT) progression in vitro. In vivo , LINC00152 overexpression significantly promoted tumour peritoneal spreading and metastasis. Mechanistic analyses indicated that LINC00152 functions as a molecular sponge for miR-138, which directly suppresses the expression of hypoxia inducible factor-1α (HIF-1α). We revealed that miR-138 is a suppressor of GBC cell metastasis and EMT progression, and a similar phenomenon was observed in HIF-1α knockdown NOZ cells. Through binding to miR-138, LINC00152 has an oncogenic effect on GBC. Overall, our study suggested that the LINC00152/miR-138/HIF-1α pathway potentiates the progression of GBC, and LINC00152 may be a novel therapeutic target.

Funder

National Natural Science Foundation of China

Publisher

The Royal Society

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience

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