In Silico Analysis of miRNA Role in Resistance of Hepatocellular Carcinoma Bel-7402 Cells to TRAIL

Zohreh Salehi; Homeyra Seydi; Paria Hadadi; Omid Tavallaei

doi:10.4103/jrptps.JRPTPS_18_19

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https://doi.org/10.4103/jrptps.JRPTPS_18_19

In Silico Analysis of miRNA Role in Resistance of Hepatocellular Carcinoma Bel-7402 Cells to TRAIL

Author(s):

Zohreh Salehi¹,

Homeyra Seydi¹,

Paria Hadadi¹,

Omid Tavallaei^2,*

1Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

2Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

Journal of Reports in Pharmaceutical Sciences:Vol. 9, issue 1; 11-8

Published online:Jun 26, 2020

Article type:Research Article

Received:Feb 21, 2019

Accepted:Dec 03, 2019

How to Cite:Zohreh SalehiHomeyra SeydiParia HadadiOmid TavallaeiIn Silico Analysis of miRNA Role in Resistance of Hepatocellular Carcinoma Bel-7402 Cells to TRAIL.J Rep Pharm Sci.9(1):e147275.https://doi.org/10.4103/jrptps.JRPTPS_18_19.

Abstract

Context: To this date, the exact basics of microRNAs (miRNAs) mechanisms in inducing a resistance to tumor necrosis factor –related apoptosis-inducing ligand (TRAIL) signaling pathways remain unclear.
Aims: The aim of this study was to analyze miRNA signaling pathways in TRAIL-resistant Bel-7402 cell line.
Materials and Methods: The Gene Expression Omnibus (GEO) database was studied for miRNA expression profiling studies in TRAIL-resistant versus TRAIL-sensitive Bel-7402 cells. By searching through databases of DIANAmT, miRanda, miRDB, miRWalk, and PICTAR using the online tools of miRWalk and TargetScan, target genes of miRNAs were predicted to express differentially by up to 50% in TRAIL-resistant versus TRAIL-sensitive Bel-7402 cells. Afterwards, signaling pathways and biological functions of miRNA target genes in TRAIL-resistant versus TRAIL-sensitive Bel-7402 cells were analyzed by the DAVID database.
Results: A total of 352 miRNAs (186 up- and 166 downregulated miRNAs) were obtained from GSE74130 GEO DataSets accession item. The upregulated miRNAs including hsamir- 145, hsa-mir-188, hsa-mir-221, hsa-mir-4802-5p, hsa-mir-198, hsa-mir-1184, and hsa-mir-345-3p were significantly intensified in apoptotic signaling pathway and process. The downregulated miRNAs including hsa-mir-138, hsa-mir-375, hsa-mir-449, hsa-mir-637, hsa-mir-208-3p, hsa-mir-4783-5p, hsamir- 548b-3p, hsa-mir-127-3p, hsa-mir-92b-5p, hsa-mir-375, hsa-mir-503-5p, hsa-mir-499a-3p, and hsamir- 154-3p were significantly raised in expression in cancer stem cell pathways.
Conclusions: Analysis of miRNA expression profile revealed that some of the upregulated miRNAs negatively contributed to the regulation of apoptosis signaling pathways and cell cycle arrest as well as promoting TRAIL-induced apoptosis resistance in TRAIL-resistant Bel-7402 cells. Also, down-regulated miRNAs were probably involved in cancer stem cell processing.

Keywords

Apoptosis

miRNA expression data

neoplasms

signaling pathways

TRAIL

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Author(s):

Zohreh Salehi:[PubMed][Scholar]
Homeyra Seydi:[PubMed][Scholar]
Paria Hadadi:[PubMed][Scholar]
Omid Tavallaei:[PubMed][Scholar]