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Adv Pharm Bull. 2024;14(1): 231-240.
doi: 10.34172/apb.2024.004
  Abstract View: 525
  PDF Download: 353

Research Article

The Simultaneous Effects of miR-145-5p and hsa-let-7a-3p on Colorectal Tumorigenesis: In Vitro Evidence

Nazila Mozammel 1 ORCID logo, Elham Baghbani 2, Mohammad Amini 2, Sheyda Jodeiry Zaer 2, Yalda Baghay Esfandyari 2, Maryam Tohidast 2, Seyed Samad Hosseini 2, Seyed Ali Rahmani 2, Ahad Mokhtarzadeh 2* ORCID logo, Behzad Baradaran 2* ORCID logo

1 Department of Biology, Higher Education Institute of Rab‐Rashid, Tabriz, Iran.
2 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
*Corresponding Authors: Ahad Mokhtarzadeh, Email: Ahad.mokhtarzadeh@gmail.com; Behzad Baradaran, Email: behzad_im@yahoo.com

Abstract

Purpose: MicroRNAs (miRNAs) are a group of small regulatory non-coding RNAs, which are dysregulated through tumor progression. let-7 and MIR-145 are both tumor suppressor microRNAs that are downregulated in a wide array of cancers including colorectal cancer (CRC).

Methods: This study was aimed to investigate the effect of simultaneous replacement of these two tumor suppressor miRNAs on proliferation, apoptosis, and migration of CRC cells. HCT-116 with lower expression levels of hsa-let-7a-3p and MIR-145-5p was selected for functional investigations. The cells were cultured and transfected with hsa-let-7a and MIR-145, separately and in combination. Cell viability and apoptosis rates were assessed by MTT assay and flow cytometry, respectively. Cell cycle status was further evaluated using flow cytometry and qRT-PCR was employed to evaluate gene expression.

Results: The obtained results showed that exogenous overexpression of MIR-145 and hsa-let-7a in HCT-116 cells could cooperatively decrease CRC cell proliferation and induce sub-G1 cell cycle arrest. Moreover, hsa-let-7a and MIR-145 co-transfection significantly increased apoptosis induction compared to separate transfected cells and control through modulating the expression levels of apoptosis-related genes including Bax, Bcl-2, P53, Caspase-3, Caspase-8, and Caspase-9. Furthermore, qRT-PCR results illustrated that hsa-let-7a and MIR-145 combination more effectively downregulated MMP-9 and MMP-2 expression, as the important modulators of metastasis, compared to the controls.

Conclusion: Taken together, considering that exogenous overexpression of MIR-145 and hsa-let-7a showed cooperative anti-cancer effects on CRC cells, their combination may be considered as a novel therapeutic strategy for the treatment of CRC.

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Submitted: 16 Nov 2022
Revision: 09 Jun 2023
Accepted: 14 Jul 2023
ePublished: 19 Jul 2023
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