Chao Guo1, Shuhuang Zhou1, Weimin Yi1, Pingzhou Yang1, Ou Li1, Jianming Liu1, Chuang Peng2. 1. Department of hepatobiliary surgery, the First Affiliated Hospital of Hunan Normal University, Hunan Provincial People's Hospital, No.61 Jiefang West Road, Changsha City, Hunan Province 410005, China. 2. Department of hepatobiliary surgery, the First Affiliated Hospital of Hunan Normal University, Hunan Provincial People's Hospital, No.61 Jiefang West Road, Changsha City, Hunan Province 410005, China. Electronic address: guochao1159@163.com.
Abstract
BACKGROUNDS/AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUNDS/AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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.
Authors: Lan Luo; Xiaoyan Hu; Aoshuang Huang; Xiaofang Liu; Lingyun Wang; Tao Du; Lei Liu; Ming Li Journal: Evid Based Complement Alternat Med Date: 2022-09-15 Impact factor: 2.650