Department of Medical Cellular Biology and Genetics, Shanxi Medical University, Taiyuan, China.
Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China.
J Cell Mol Med. 2023 Aug;27(15):2112-2122. doi: 10.1111/jcmm.17798. Epub 2023 Jun 1.
miR-138-5p has been identified as a novel cancer-related miRNA molecule in a variety of malignancies. However, the functions and mechanisms underlying miR-138-5p in colorectal carcinoma (CRC) remains largely unknown. In the present study, we analysed the biological effects and clinical significance of miR-138-5p in CRC. miR-138-5p expression was analysed by quantitative real-time PCR in CRC tissues and cell lines. The effects of miR-138-5p on CRC cell growth was detected by cell proliferation, colony formation, cell cycle and cell apoptosis assays in vitro and in vivo. Our data showed that miR-138-5p was significantly downregulated in CRC. Downregulated miR-138-5p was related with poor prognosis in patients with CRC. miR-138-5p suppressed CRC growth but promoted cell death both in vitro and in vivo. Online predictions and integrated experiments identified that miR-138-5p targeted MCU, and downregulated miR-138-5p promoted mitochondrial biogenesis in CRC. In the light of the underlying mechanisms, our results indicated that downregulated miR-138-5p led to increased expression of MCU, which subsequently increased the production of ROS to promote CRC growth. Our results indicated that downregulated miR-138-5p strengthened mitochondrial biogenesis through targeting MCU, thus contributing to CRC cell growth, which may provide a potential therapeutic target for CRC.
miR-138-5p 已被鉴定为多种恶性肿瘤中一种新的癌症相关 miRNA 分子。然而，miR-138-5p 在结直肠癌（CRC）中的功能和机制仍知之甚少。在本研究中，我们分析了 miR-138-5p 在 CRC 中的生物学效应和临床意义。通过定量实时 PCR 分析 CRC 组织和细胞系中的 miR-138-5p 表达。通过体外和体内细胞增殖、集落形成、细胞周期和细胞凋亡实验检测 miR-138-5p 对 CRC 细胞生长的影响。我们的数据表明，miR-138-5p 在 CRC 中显著下调。下调的 miR-138-5p 与 CRC 患者的预后不良相关。miR-138-5p 抑制 CRC 生长，但在体外和体内均促进细胞死亡。在线预测和综合实验表明，miR-138-5p 靶向 MCU，下调的 miR-138-5p 促进 CRC 中的线粒体生物发生。根据潜在的机制，我们的结果表明，下调的 miR-138-5p 导致 MCU 的表达增加，进而增加 ROS 的产生以促进 CRC 生长。我们的结果表明，下调的 miR-138-5p 通过靶向 MCU 增强线粒体生物发生，从而促进 CRC 细胞生长，这可能为 CRC 提供一个潜在的治疗靶点。
