Wang Juan, Lai Zonglang, Liu Na, Wang Yuhong, Li Feng, Song Na, Cheng Jun
Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, China.
Hereditas. 2025 Mar 28;162(1):46. doi: 10.1186/s41065-025-00395-7.
Although increasing evidence suggests that microRNAs (miRNAs) play different roles in the occurrence, development, and prognosis of colorectal cancer (CRC), investigations on miRNA-targeted regulation in CRC are sparse. However, the high morbidity and mortality of CRC necessitates exploring this area of research for potential alternative therapeutic approaches to CRC.
Bioinformatics analysis was used to obtain the key Hub genes related to CRC, and survival analysis was performed to screen out the core genes. Meanwhile, verification was performed using CCK-8, Transwell, qPCR, WB, immunohistochemistry and dual luciferase assays at a cellular level.
This study identified the hub gene KLK6 associated with CRC based on the GEO and TCGA databases. Survival analysis revealed a significant decrease in the survival rate of CRC patients with increasing expression levels of KLK6. Target gene prediction confirmed that miR-431-5p can target KLK6. Cell experimental results demonstrated that the miR-431-5p inhibitor enhanced cell viability and promoted cell migration and invasion while miR-431-5p mimics reduced cell viability and inhibited cell migration and invasion. Both the inhibitor and mimics of miR-431-5p suppressed and promoted the expression of miR-431-5p, as well as promoted and inhibited the KLK6 mRNA and protein expression. Dual luciferase results showed that miR-431-5p targeted KLK6, and cell recovery experiments further verified that miR-431-5p regulated cell viability, migration and invasion by targeting KLK6.
Through target gene prediction, miR-431-5p was found to target KLK6, suggesting its therapeutic potential in CRC. As such, therapies that can inhibit KLK6 via miR-431-5p offer a promising approach to CRC.
Not applicable.
尽管越来越多的证据表明微小RNA（miRNA）在结直肠癌（CRC）的发生、发展和预后中发挥着不同作用，但关于CRC中miRNA靶向调控的研究却很少。然而，CRC的高发病率和死亡率使得有必要探索这一研究领域，以寻找潜在的CRC替代治疗方法。
采用生物信息学分析获取与CRC相关的关键枢纽基因，并进行生存分析以筛选出核心基因。同时，在细胞水平上使用CCK-8、Transwell、qPCR、WB、免疫组织化学和双荧光素酶测定进行验证。
本研究基于GEO和TCGA数据库鉴定出与CRC相关的枢纽基因KLK6。生存分析显示，随着KLK6表达水平的升高，CRC患者的生存率显著降低。靶基因预测证实miR-431-5p可以靶向KLK6。细胞实验结果表明，miR-431-5p抑制剂增强了细胞活力，促进了细胞迁移和侵袭，而miR-431-5p模拟物降低了细胞活力，抑制了细胞迁移和侵袭。miR-431-5p的抑制剂和模拟物均抑制和促进了miR-431-5p的表达，同时促进和抑制了KLK6 mRNA和蛋白表达。双荧光素酶结果显示miR-431-5p靶向KLK6，细胞拯救实验进一步验证了miR-431-5p通过靶向KLK6调节细胞活力、迁移和侵袭。
通过靶基因预测，发现miR-431-5p靶向KLK6，提示其在CRC中的治疗潜力。因此，通过miR-431-5p抑制KLK6的疗法为CRC提供了一种有前景的治疗方法。
不适用。
