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通过两种潜在药物靶点直接结合减轻miR-629-5p和miR-660-5p的致癌作用以预防结直肠癌

Mitigating the Oncogenic Roles of miR-629-5p and miR-660-5p Through Direct Binding by Two Potential Drug Targets for Colorectal Cancer Prevention.

作者信息

Poorbaferani Fariborz, Bolandi Soheil, Abdolvand Mohammad, Aghaie-Kheyrabadi Fatemeh, Farhadian Nooshin, Abdolvand Shirin, Maghool Fatemeh, Emami Mohammad H, Fahim Alireza, Rahimi Hojjatolah, Amjadi Elham, Bon Fatemeh D N, Hemati Simin, Salehi Mansoor

机构信息

Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Int J Prev Med. 2025 May 28;16:33. doi: 10.4103/ijpvm.ijpvm_277_24. eCollection 2025.

DOI:10.4103/ijpvm.ijpvm_277_24
PMID:40520033
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12165612/
Abstract

BACKGROUND

Many studies have reported the oncogenic roles of microRNA (miRNA)-629-5p and miRNA-660-5p in various cancers. This study aimed to elucidate the oncogenic roles of miRNA-629-5p and miRNA-660-5p, focusing on their potential contributions to early colorectal cancer (CRC) detection. Additionally, this research examines the efficacy of Regorafenib and 3,3'-diindolylmethane (DIM) as therapeutic agents aimed at mitigating the oncogenic activities of these miRNAs by influencing their structural and conformational dynamics, thereby offering a preventive strategy against CRC.

METHODS

The study utilized quantitative real-time polymerase chain reaction (QRT-PCR) to confirm the overexpression of miR-629-5p and miR-660-5p in 40 CRC tissues compared to 40 standard samples and their association with clinicopathological factors. Molecular docking and molecular dynamics simulation were used to investigate Regorafenib and DIM binding modes to miR-629-5p and miR-660-5p.

RESULTS

QRT-PCR showed that miR-629-5p and miR-660-5p were overexpressed in CRC tissues. In silico molecular docking and dynamic simulation strengthened our hypothesis that Regorafenib and DIM were located in the structures of the mentioned miRNAs, resulting in a slight alteration in their structures during the interaction process.

CONCLUSIONS

The study's findings suggest that miR-629-5p and miR-660-5p may have potential as predictive biomarkers and treatment targets for Preventing CRC and that Regorafenib and DIM may have miRNA binding properties. They indicated a high affinity to miRNA-629-5p compared with miRNA-660-5p created a slight change in its structure and can suppress its activity in CRC. However, extra experimental approaches are needed to approve our hypothesis.

摘要

背景

许多研究报道了微小RNA(miRNA)-629-5p和miRNA-660-5p在各种癌症中的致癌作用。本研究旨在阐明miRNA-629-5p和miRNA-660-5p的致癌作用,重点关注它们对早期结直肠癌(CRC)检测的潜在贡献。此外,本研究还考察了瑞戈非尼和3,3'-二吲哚甲烷(DIM)作为治疗药物的疗效,旨在通过影响这些miRNA的结构和构象动力学来减轻其致癌活性,从而提供一种预防CRC的策略。

方法

本研究利用定量实时聚合酶链反应(QRT-PCR)来确认与40个标准样本相比,40个CRC组织中miR-629-5p和miR-660-5p的过表达情况及其与临床病理因素的关联。采用分子对接和分子动力学模拟来研究瑞戈非尼和DIM与miRNA-629-5p和miRNA-660-5p的结合模式。

结果

QRT-PCR显示miR-629-5p和miR-660-5p在CRC组织中过表达。计算机模拟分子对接和动态模拟强化了我们的假设,即瑞戈非尼和DIM位于上述miRNA的结构中,在相互作用过程中导致其结构略有改变。

结论

该研究结果表明,miR-629-5p和miR-660-5p可能具有作为预防CRC的预测生物标志物和治疗靶点的潜力,并且瑞戈非尼和DIM可能具有miRNA结合特性。与miRNA-660-5p相比,它们对miRNA-629-5p具有更高的亲和力,使其结构发生轻微变化,并可抑制其在CRC中的活性。然而,需要额外的实验方法来验证我们的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/6df4a9d9bdcf/IJPVM-16-33-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/e1f1490061bd/IJPVM-16-33-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/8575862a1ac0/IJPVM-16-33-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/b2b3443f7d45/IJPVM-16-33-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/221057ddf37f/IJPVM-16-33-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/06c06764cdc1/IJPVM-16-33-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/6df4a9d9bdcf/IJPVM-16-33-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/e1f1490061bd/IJPVM-16-33-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/8575862a1ac0/IJPVM-16-33-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/b2b3443f7d45/IJPVM-16-33-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/221057ddf37f/IJPVM-16-33-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/06c06764cdc1/IJPVM-16-33-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c9/12165612/6df4a9d9bdcf/IJPVM-16-33-g006.jpg

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