Long non-coding RNA muskelin 1 antisense RNA (MKLN1-AS) is a potential diagnostic and prognostic biomarker and therapeutic target for hepatocellular carcinoma

• Published in: Experimental and molecular pathology Vol. 120; p. 104638
• Main Authors: Guo, Chao, Zhou, Shuhuang, Yi, Weimin, Yang, Pingzhou, Li, Ou, Liu, Jianming, Peng, Chuang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.06.2021
• Subjects: Hepatocarcinogenesis; Hepatocellular carcinoma; MKLN1-AS; YAP1; YAP1; Hepatocellular carcinoma; Hepatocarcinogenesis; MKLN1-AS
• ISSN: 0014-4800; 1096-0945; 1096-0945
• DOI: 10.1016/j.yexmp.2021.104638

Hepatocellular carcinoma is recognized as the most common subtype of hepatic cancer. Muskelin 1 antisense RNA (MKLN1-AS) shows prognostic value in hepatitis B virus-hepatocellular carcinoma. The aim of this study is to investigate the detailed biological role of MKLN1-AS and Yes-associated transcriptional regulator 1 (YAP1)-related mechanisms. Based on online databases (GEPIA, TCGA, and GEO), the expression of MKLN1-AS and YAP1 in patients with hepatocellular carcinoma was analyzed. The IntaRNA algorithm was used to predict complementary sites between MKLN1-AS and YAP1 mRNA. Hepatocellular carcinoma tumor tissues and cells were collected for the quantification of MKLN1-AS and YAP1. FISH was performed to explore the location of MKLN1-AS in cells. The effects of MKLN1-AS and YAP1 on proliferation, migration and invasionof hepatocellular carcinoma were determined in vitro and in vivo. Actinomycin D and RNA immunoprecipitation were resorted to confirm the regulatory role of MKLN1-AS in YAP1 expression. The up-regulation of MKLN1-AS contributed to the poor prognosis of patients with hepatocellular carcinoma. MKLN1-AS and YAP1 were overexpressed in hepatocellular carcinoma tissues and cells. MKLN1-AS positively modulated YAP1 expression through targeting and stabilizing YAP1 mRNA.MKLN1-AS was predominantly located in the cytoplasm of the cells. MKLN1-AS intensified proliferation, migration and invasion of hepatocellular carcinoma cells via YAP1. MKLN1-AS also caused hepatocarcinogenesis through inducing YAP1 expression in vivo. MKLN1-AS overexpression enhances the stability of YAP1 mRNA, which is necessary for the oncogenic activity of MKLN1-AS. MKLN1-AS can be utilized in the diagnosis and prognosis of hepatocellular carcinoma as an upstream factor of YAP1. •MKLN1-AS and YAP1 are overexpressed in hepatocellular carcinoma;•MKLN1-AS up-regulates YAP1 expression through stabilizing YAP1 mRNA;•MKLN1-AS shows oncogenic effects in synergy with YAP1.