通过PFKFB3靶向研究MicroRNA-519d-3p在提高结直肠癌细胞对5-氟尿嘧啶化疗敏感性中的作用

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

摘要

目的化疗耐药是结直肠癌（CRC）防治的主要障碍。因此，确定有效的生物标志物治疗方法势在必行。尽管microrna （miRs）在耐药中起着至关重要的作用，但miR-519d-3p在结直肠癌耐药中的作用机制尚不完全清楚。因此，本研究旨在探讨miR-519d-3p在CRC细胞对5-氟尿嘧啶（5-FU）的化学敏感性中的生物学功能。方法用5-FU处理scrc细胞并转染。观察细胞增殖、侵袭和凋亡情况。我们分析了miR-519d-3p与6-磷酸果糖激酶-2/果糖- 2,6 -双磷酸酶-3 （PFKFB3）的关系，并进一步研究了它们在结直肠癌中的相互作用。通过体内肿瘤实验研究miR-519d-3p和5-FU在结直肠癌中的功能。结果在体外实验中，过表达miR-519d-3p的CRC细胞对5-FU更敏感，因为miR-519d-3p抑制增殖和侵袭，刺激细胞凋亡。miR-519d-3p直接靶向PFKFB3。在结直肠癌细胞中，PFKFB3过表达挽救了mir -519d-3p诱导的5-FU毒性。体内实验结果显示，miR-519d-3p模拟物和5-FU共同处理的小鼠显示出更高的抗肿瘤活性。综上所述，靶向miR-519d-3p和PFKFB3可能改善CRC细胞的5-FU化疗敏感性。

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

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.