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Adv Pharm Bull. 2020;10(3): 444-451.
doi: 10.34172/apb.2020.054
  Abstract View: 60
  PDF Download: 43

Research Article

miR-330 Regulates Colorectal Cancer Oncogenesis by Targeting BACH1

Solmaz Shirjang 1 ORCID logo, Behzad Mansoori 1,2,3, Ali Mohammadi 1, Neda Shajari 4, Pascal H.G. Duijf 5, Souzan Najafi 1, Fereydoon Abedi Gaballu 1, Katayoon Nofouzi 6, Behzad Baradaran 1 * ORCID logo

1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
4 Department of Immunology, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran.
5 University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Australia.
6 Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

Abstract

Purpose: Based on WHO report, colorectal cancer (CRC) is the second cause of death amongpatients with cancer worldwide. Dysregulation of miRNAs expressions has been demonstratedin different human cancers, especially CRC. Studies have shown that miR-330 could act as bothTS-miR and/or oncomiR in different types of cancers. BACH1 is also identified as a transcriptionfactor, which is involved in ontogenesis. In this study, we evaluated the CRC suppression viasilencing of BACH1 by small silencer molecule called miR-330.Methods: Firstly, we analyzed the BACH1, miR-330-3p and miR-330-5p expressions according tothe colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) project established froma patient of the colon and rectal cancer patients in The Cancer Genome Atlas (TCGA) database.The targeting of BACH1 via miR-330 in human CRC cells was evaluated by Vejnar bioinformaticsmethods, and confirmed by qRT-PCR and western blot analysis. Proliferation was performed byMTT assay. The MMP9, CXCR4, and VEGFR proteins were measured by western blotting.Results: The analysis of BACH1, miR-330-3p, and miR-330-5p expressions according to theCOAD and READ projects showed that BACH1 was overexpressed, but miR-330-3p and miR-330-5p were reduced in CRC tumors compared to normal controls. The miR-330 inductionprevented proliferation of CRC cell by targeting BACH1 mRNA, which represses MMP9, C-X-Cchemokine receptor type 4 (CXCR4), and vascular endothelial growth factor receptor (VEGFR)proteins expressions.Conclusion: Our results suggested that BACH1 is a potential target for miR-330 in CRC cells.The miR-330 induction inhibits CRC cells proliferation by suppressing BACH1 expression inposttranscriptional level. It was suggested that targeting of BACH1 via miRNA such as miR-330could be a valid strategy in the field of CRC targeted therapy via modulating the oncogenicsignaling pathway.
Keywords: miR-330, BACH1, MMP9, CXCR4, VEGFR, Proliferation, Colorectal cancer
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Submitted: 28 Aug 2019
Revision: 28 Nov 2019
Accepted: 08 Dec 2019
ePublished: 11 May 2020
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