Simultaneous suppression of miR-21 and restoration of miR-145 in gastric cancer cells; a promising strategy for inhibition of cell proliferation and migration.

IF 2.2 4区工程技术 Q3 PHARMACOLOGY & PHARMACY

Bioimpacts Pub Date : 2024-01-01 Epub Date: 2023-08-27 DOI:10.34172/bi.2023.27764

Farzaneh Bilan, Mohammad Amini, Mohammad Amin Doustvandi, Maryam Tohidast, Amir Baghbanzadeh, Seyed Samad Hosseini, Ahad Mokhtarzadeh, Behzad Baradaran

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引用次数: 0

Abstract

Introduction: Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. microRNAs are a group of regulatory non-coding RNAs that are involved in GC progression. miR-145 as a tumor suppressor and miR-21 as an oncomiR were shown to be dysregulated in many cancers including GC. This research aimed to enhance the expression of miR-145 while reducing the expression of miR-21 and examine their impact on the proliferation, apoptosis, and migration of GC cells.

Methods: KATO III cells with high expression levels of miR-21-5p and low expression of miR-145-5p were selected. These cells were then transfected with either miR-145-5p mimics or anti-miR-21-5p, alone or in combination. Afterward, the cell survival rate was determined using the MTT assay, while apoptosis induction was investigated through V-FITC/PI and DAPI staining. Additionally, cell migration was examined using the wound healing assay, and cell cycle progression was analyzed through flow cytometry. Furthermore, gene expression levels were quantified utilizing the qRT-PCR technique.

Results: The study's findings indicated that the co-replacement of miR-145-5p and anti-miR-21-5p led to a decrease in cell viability and the induction of apoptosis in GC cells. This was achieved via modulating the expression of Bax and Bcl-2, major cell survival regulators. Additionally, the combination therapy significantly increased sub-G1 cell cycle arrest and reduced cell migration by downregulating MMP-9 expression as an epithelial-mesenchymal transition marker. This study provides evidence for the therapeutic possibility of the combination of miR-145-5p and anti-miR-21-5p and also suggests that they could inhibit cell proliferation by modulating the PTEN/AKT1 signaling pathway.

Conclusion: Our research revealed that utilizing miR-145-5p and anti-miR-21-5p together could be a promising therapeutic approach for treating GC.

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胃癌细胞中miR-21的同时抑制和miR-145的恢复抑制细胞增殖和迁移的一种有前途的策略

导言:在世界范围内，胃癌(GC)是癌症相关死亡的第三大原因。microRNAs是一组参与GC进展的调控非编码rna。作为肿瘤抑制因子的miR-145和作为肿瘤抑制因子的miR-21在包括胃癌在内的许多癌症中被证明是失调的。本研究旨在提高miR-145的表达，降低miR-21的表达，并研究其对胃癌细胞增殖、凋亡和迁移的影响。方法:选择miR-21-5p高表达、miR-145-5p低表达的KATO III细胞。然后用miR-145-5p模拟物或anti-miR-21-5p单独或联合转染这些细胞。MTT法测定细胞存活率，V-FITC/PI和DAPI染色观察细胞凋亡诱导情况。此外，使用伤口愈合试验检测细胞迁移，并通过流式细胞术分析细胞周期进展。此外，利用qRT-PCR技术量化基因表达水平。结果:本研究结果表明，miR-145-5p和anti-miR-21-5p共同替代导致GC细胞活力下降，诱导细胞凋亡。这是通过调节主要细胞存活调节因子Bax和Bcl-2的表达实现的。此外，联合治疗通过下调MMP-9(上皮-间质转化标志物)的表达，显著增加亚g1细胞周期阻滞，减少细胞迁移。本研究为miR-145-5p和anti-miR-21-5p联合治疗提供了证据，也表明它们可以通过调节PTEN/AKT1信号通路抑制细胞增殖。结论:我们的研究表明，联合使用miR-145-5p和anti-miR-21-5p可能是治疗胃癌的一种有希望的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioimpacts Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

4.80

自引率

7.70%

发文量

审稿时长

5 weeks

期刊介绍： BioImpacts (BI) is a peer-reviewed multidisciplinary international journal, covering original research articles, reviews, commentaries, hypotheses, methodologies, and visions/reflections dealing with all aspects of biological and biomedical researches at molecular, cellular, functional and translational dimensions.