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Long noncoding RNA NEAT1 suppresses sorafenib sensitivity of hepatocellular carcinoma cells via regulating miR‐335–c‐Met
Author(s) -
Chen Shuwei,
Xia Xinhu
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27567
Subject(s) - gene knockdown , viability assay , cancer research , sorafenib , apoptosis , small hairpin rna , gene silencing , rna interference , biology , microbiology and biotechnology , cell growth , long non coding rna , microrna , protein kinase b , chemistry , hepatocellular carcinoma , rna , gene , biochemistry
Objectives To investigate the role of long noncoding RNA (lncRNA) nuclear‐enriched abundant transcript 1 (NEAT1) in regulating sorafenib (Sora) sensitivity of hepatocellular carcinoma (HCC) cells and possible signaling pathways. Methods HCC cell lines and tumor tissue were quantified for NEAT1 expression by quantitative polymerase chain reaction (qPCR). Following shRNA (short hairpin RNA) knockdown of NEAT1, cell viability, apoptosis, and related protein expression were measured after drug treatment. The downstream target of NEAT1, including miR‐335 and c‐Met was studied using a combination of luciferase binding assay, gene knockdown/overexpression, western blot analysis, and cell viability/apoptosis assay. Cancer cells with NEAT1 knockdown were transplanted onto nude mice for in vivo tumorigenesis assay. Results Silencing of NEAT1 in HCC cells facilitated Sora sensitivity by enhancing drug‐induced apoptosis, and led to smaller tumor size on nude mice. Mechanistic study suggested that miR‐335 was negatively regulated by NEAT1, and miR‐335 further suppressed c‐Met–Akt pathway, whose activation caused drug resistance of HCC cells. The knockdown of miR‐335, or overexpression of c‐Met, all remarkably abolished the proapoptotic effect of NEAT1 knockdown in HCC cells. Conclusion lncRNA NEAT1 mediates Sora resistance of HCC cells by suppressing miR‐335 expression, and disinhibition on c‐Met–Akt signaling pathway. Our results provide potency of NEAT1 as the biomarker for drug resistant HCC and possible treating targets.