In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells  

作　　者：Patricia de la Cruz-Ojeda Ester Parras-Martínez Raquel Rey-Pérez Jordi Muntané 

机构地区：[1]Functional Genomics of Solid Tumors Laboratory,Centre de Recherche des Cordeliers,Paris 75006,France [2]Department of Oncology Surgery,Cell Therapy and Organ Transplantation,Institute of Biomedicine of Seville,Virgen del Rocio University Hospital,Seville 41013,Spain [3]Biomedical Research Center for Hepatic and Digestive Diseases,CIBERehd,Madrid 28029,Spain [4]Department of Medical Physiology and Biophysics,University of Seville,Seville 41009,Spain

出　　处：《World Journal of Gastroenterology》2025年第3期84-102,共19页世界胃肠病学杂志（英文）

基　　金：Supported by Instituto de Salud Carlos III(ISCiii),No.PI19/01266 and No.PI22/00857;Consejería de Salud y Familias(Junta de Andalucía),No.PI-0216-2020 and No.PIP-0215-2020;Biomedical Research Network Center for Liver and Digestive Diseases(CIBERehd)founded by the ISCIII and co-financed by European Regional Development Fund“A way to achieve Europe”ERDF.

摘　　要：BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology worldwide.Sorafenib is still a recommended treatment for a large proportion of patients with advanced HCC.Different patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 cells.AIM To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 cells.Various available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 cells.METHODS HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 hours.Total RNA,including small and long RNA,was extracted with a commercial miRNeasy kit.RNAseq was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory axes.RESULTS MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 cells.SNHG12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 cells.The axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib treatment.CONCLUSION Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关 键 词：Cell culture Hepatocellular carcinoma Non-coding RNA RNASEQ SORAFENIB 

分 类 号：R735.34[医药卫生—肿瘤]