Wang Dequan, Wang Jielian, Yao Fei, Xie Zhufu, Wu Jianze, Chen Huiguang, Wu Qingming
Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, China.
Department of Internal Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China.
PLoS One. 2024 Dec 31;19(12):e0309979. doi: 10.1371/journal.pone.0309979. eCollection 2024.
The effectiveness of chemotherapy involving 5-fluorouracil and cisplatin (DDP) for the treatment of colorectal cancer (CRC) is often limited due to the emergence of drug resistance. An increasing body of research highlights the crucial role of abnormally expressed microRNAs (miR/miRNAs) in fostering drug resistance in various types of cancer. The present study was the first to explore the potential roles and mechanisms of the small non-coding RNA miR-1247-3p in CRC, particularly its association with DDP resistance in CRC. The findings of the current study revealed a significant decrease in miR-1247-3p expression in CRC cells, especially those resistant to drugs. By contrast, there was a marked increase in the expression of cyclin D1 (CCND1), a known target gene of miR-1247-3p that is negatively regulated by this miRNA. By modulating CCND1, miR-1247-3p can effectively reduce drug resistance and promote apoptosis in CRC cells, suggesting that miR-1247-3p could potentially reduce chemotherapy resistance by targeting CCND1. These results highlight the pivotal role of miR-1247-3p in reducing chemotherapy resistance through the inhibition of CCND1, providing insight into a promising therapeutic strategy for overcoming CRC resistance.
由于耐药性的出现，涉及5-氟尿嘧啶和顺铂（DDP）的化疗对结直肠癌（CRC）的治疗效果往往有限。越来越多的研究强调了异常表达的微小RNA（miR/miRNAs）在促进各类癌症耐药性方面的关键作用。本研究首次探讨了小非编码RNA miR-1247-3p在结直肠癌中的潜在作用和机制，特别是其与结直肠癌顺铂耐药性的关联。当前研究结果显示，结直肠癌细胞中miR-1247-3p表达显著降低，尤其是那些对药物耐药的细胞。相比之下，细胞周期蛋白D1（CCND1）的表达显著增加，CCND1是miR-1247-3p的已知靶基因，受该miRNA负调控。通过调节CCND1，miR-1247-3p可有效降低结直肠癌细胞的耐药性并促进其凋亡，这表明miR-1247-3p可能通过靶向CCND1来降低化疗耐药性。这些结果突出了miR-1247-3p通过抑制CCND1在降低化疗耐药性方面的关键作用，为克服结直肠癌耐药性提供了一种有前景的治疗策略。
