长非编码RNA muskelin 1反义RNA（MKLN1-AS）是肝细胞癌的潜在诊断

StephenW

Long non-coding RNA muskelin 1 antisense RNA (MKLN1-AS) is a potential diagnostic and prognostic biomarker and therapeutic target for hepatocellular carcinoma
Chao Guo  1 , Shuhuang Zhou  1 , Weimin Yi  1 , Pingzhou Yang  1 , Ou Li  1 , Jianming Liu  1 , Chuang Peng  2
Affiliations
Affiliations

    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: [email protected].

    PMID: 33878313 DOI: 10.1016/j.yexmp.2021.104638

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.

Keywords: Hepatocarcinogenesis; Hepatocellular carcinoma; MKLN1-AS; YAP1.

Copyright © 2021. Published by Elsevier Inc.

StephenW

长非编码RNA muskelin 1反义RNA（MKLN1-AS）是肝细胞癌的潜在诊断和预后生物标志物和治疗靶标
郭超1，周曙煌1，魏敏义1，杨平洲1，欧丽1，刘建明1，庄鹏2
隶属关系
隶属关系

    1个
    湖南省师范大学附属第一医院肝胆外科，湖南省人民医院，湖南长沙市解放西路61号410005
    2个
    湖南省师范大学附属第一医院肝胆外科，湖南省人民医院，湖南长沙市解放西路61号410005电子地址：[email protected]。

    PMID：33878313 DOI：10.1016 / j.yexmp.2021.104638

抽象的

背景/目的：肝细胞癌被认为是最常见的肝癌亚型。 Muskelin 1反义RNA（MKLN1-AS）在乙型肝炎病毒-肝细胞癌中具有预后价值。这项研究的目的是调查MKLN1-AS和与Yes相关的转录调节因子1（YAP1）相关的机制的详细生物学作用。

方法：基于在线数据库（GEPIA，TCGA和GEO），分析MKLN1-AS和YAP1在肝细胞癌患者中的表达。 IntaRNA算法用于预测MKLN1-AS和YAP1 mRNA之间的互补位点。收集肝细胞癌肿瘤组织和细胞以定量MKLN1-AS和YAP1。进行了FISH探索MKLN1-AS在细胞中的位置。在体外和体内测定了MKLN1-AS和YAP1对肝细胞癌增殖，迁移和侵袭的影响。采取放线菌素D和RNA免疫沉淀来确认MKLN1-AS在YAP1表达中的调节作用。

结果：MKLN1-AS的上调导致肝细胞癌患者预后不良。 MKLN1-AS和YAP1在肝细胞癌组织和细胞中过表达。 MKLN1-AS通过靶向和稳定YAP1 mRNA来积极调节YAP1的表达。MKLN1-AS主要位于细胞的细胞质中。 MKLN1-AS通过YAP1增强肝细胞癌细胞的增殖，迁移和侵袭。 MKLN1-AS还通过在体内诱导YAP1表达而引起肝癌发生。

结论：MKLN1-AS的过表达增强了YAP1 mRNA的稳定性，这对于MKLN1-AS的致癌活性是必需的。 MKLN1-AS可作为YAP1的上游因子用于肝细胞癌的诊断和预后。

关键字：肝癌发生；肝细胞癌； MKLN1-AS； YAP1。

版权所有©2021. Elsevier Inc.发行。