de la Cruz-Ojeda P, Parras-Martínez E, Rey-Pérez R, Muntané J. In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells. World J Gastroenterol 2025; 31(3): 95207 [DOI: 10.3748/wjg.v31.i3.95207]
Corresponding Author of This Article
Jordi Muntané, PhD, Department of Oncology Surgery, Cell Therapy and Organ Transplantation, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, Avn. Manuel Siurot S/N, Seville 41013, Spain. jmuntane-ibis@us.es
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jan 21, 2025; 31(3): 95207 Published online Jan 21, 2025. doi: 10.3748/wjg.v31.i3.95207
In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells
Patricia de la Cruz-Ojeda, Ester Parras-Martínez, Raquel Rey-Pérez, Jordi Muntané
Patricia de la Cruz-Ojeda, Functional Genomics of Solid Tumors Laboratory, Centre de Recherche des Cordeliers, Paris 75006, France
Patricia de la Cruz-Ojeda, Ester Parras-Martínez, Raquel Rey-Pérez, Jordi Muntané, Department of Oncology Surgery, Cell Therapy and Organ Transplantation, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, Seville 41013, Spain
Patricia de la Cruz-Ojeda, Jordi Muntané, Biomedical Research Center for Hepatic and Digestive Diseases, CIBERehd, Madrid 28029, Spain
Jordi Muntané, Department of Medical Physiology and Biophysics, University of Seville, Seville 41009, Spain
Author contributions: de la Cruz-Ojeda P performed the research, contributed to the implementation of analytical tools and edited the manuscript; Parras-Martínez E and Rey-Pérez R analyzed data; Muntané J designed the research, wrote the paper, and obtained funding. All authors have read and approved the final manuscript.
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.
Institutional review board statement: This study is based on the use of the HepG2 and SNU449 cell lines. The study did not require an Institutional review board.
Institutional animal care and use committee statement: This study is based on the use of HepG2 and SNU449 cell lines. The study did not require an Institutional Animal Care and Use Committee approval form.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data will be freely available according to the requirement of the WJG as an open-access article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jordi Muntané, PhD, Department of Oncology Surgery, Cell Therapy and Organ Transplantation, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, Avn. Manuel Siurot S/N, Seville 41013, Spain. jmuntane-ibis@us.es
Received: April 4, 2024 Revised: August 30, 2024 Accepted: September 12, 2024 Published online: January 21, 2025 Processing time: 259 Days and 21.6 Hours
Abstract
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 (10 μmol/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/hsa-mir-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.
Core Tip: In the current study, we investigated the differential lncRNA-miRNA-mRNA regulatory axes in HepG2 and SNU449 under Sorafenib treatment. The study identified lncRNA-miRNA regulatory axes leading to increased expression mRNA with positive (SMAD7, TIRARP, TFAP4, FAXDC2 and ADRB2) and negative (VEGFA) therapeutic effects in HepG2 and SNU449 under Sorafenib treatment.
