Investigating the role of MicroRNA-519d-3p in enhancing chemosensitivity of colorectal cancer cells to 5-Fluorouracil through PFKFB3 targeting

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics Pub Date : 2025-01-01 DOI:10.1016/j.clinsp.2025.100606

Yangyang Zhang , Yiqing Zhang , Yanan Xiao , Shufen Xu , Jie Li , Juan Li , Lisha Chang , Jie Ding , Di Wu , Li Wang , Guangxu Xu , Keming Wang

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引用次数: 0

Abstract

Objective

In the fight against Colorectal Cancer (CRC), chemotherapy resistance is a major obstacle. Therefore, it is imperative to identify effective biomarker therapeutics. Despite microRNAs (miRs) playing a crucial role in drug resistance, the mechanisms comprising miR-519d-3p's role in CRC drug resistance have not been fully understood. Therefore, the present study aimed to investigate the biological function of miR-519d-3p in the chemosensitivity of CRC cells to 5-Fluorouracil (5-FU).

Methods

CRC cells were treated with 5-FU and transfected. Cellular proliferation, invasion, and apoptosis were evaluated. The relationship between miR-519d-3p and 6-Phosphofructokinase-2/Frucose-2, 6-Biphosphatase-3 (PFKFB3) was analyzed, and their interaction in CRC was further investigated. In vivo tumor experiments were conducted to investigate the function of miR-519d-3p and 5-FU in CRC.

Results

As determined, CRC cells overexpressing miR-519d-3p were more sensitive to 5-FU in vitro, as miR-519d-3p inhibits proliferation and invasion and stimulates apoptosis. miR-519d-3p directly targeted PFKFB3. In CRC cells, PFKFB3 overexpression rescued miR-519d-3p-induced 5-FU toxicity. In vivo results showed that mice co-treated with miR-519d-3p mimics and 5-FU showed higher antitumor activity.

Conclusion

Overall, it may be possible to improve 5-FU chemosensitivity of CRC cells by targeting miR-519d-3p and PFKFB3.

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来源期刊

Clinics 医学-医学：内科

CiteScore

4.10

自引率

3.70%

发文量

129

审稿时长

52 days

期刊介绍： CLINICS is an electronic journal that publishes peer-reviewed articles in continuous flow, of interest to clinicians and researchers in the medical sciences. CLINICS complies with the policies of funding agencies which request or require deposition of the published articles that they fund into publicly available databases. CLINICS supports the position of the International Committee of Medical Journal Editors (ICMJE) on trial registration.