Background/Objectives: Keratins form a crucial component of the epithelial cytoskeleton, playing an essential role in maintaining tissue architecture and coordinating key cellular functions. KRT80 is a type II keratin that has emerged as an oncogenic driver in several malignancies, yet its involvement in colorectal cancer (CRC) remains unclear. Here, we investigated the molecular interaction between miR-195-5p, KRT80 expression, and CRC growth. Methods: Potential miR-195-5p binding sites in the KRT80 3′-UTR were identified through the use of integrated bioinformatic analyses, while publicly available datasets confirmed a significant overexpression of KRT80 in CRC tissues compared to normal mucosa. This finding was further validated through the use of mRNA and protein analysis in paired tumor and adjacent normal samples from CRC patients. Results: Functional assays involving CRC cell lines showed that transfection with miR-195-5p mimics led to a significant downregulation of KRT80 expression, reflecting the effects of direct KRT80 silencing by siRNA. Both molecular approaches induced G1-phase cell cycle arrest, concomitantly with reductions in G2/M populations. Furthermore, the in vivo delivery of miR-195-5p mimics in a mouse model of colitis-associated CRC resulted in a significant reduction inKrt80expression in the colon. Conclusions: Collectively, our results reveal that miR-195-5p negatively regulates KRT80 expression, contributing to its tumor-suppressive activity in colorectal cancer and highlighting a molecular mechanism with potential therapeutic relevance.
背景/目的：角蛋白是上皮细胞骨架的关键组成部分，在维持组织结构完整性和协调关键细胞功能中发挥重要作用。KRT80作为II型角蛋白，已在多种恶性肿瘤中被证实具有致癌驱动作用，但其在结直肠癌（CRC）中的具体作用机制尚不明确。本研究旨在探讨miR-195-5p与KRT80表达之间的分子相互作用及其对结直肠癌生长的影响。方法：通过整合生物信息学分析，我们识别出KRT80基因3′-UTR区域潜在的miR-195-5p结合位点。公共数据库分析显示，与正常黏膜组织相比，KRT80在结直肠癌组织中显著高表达，这一发现在结直肠癌患者的配对肿瘤与癌旁正常组织样本中，通过mRNA和蛋白质水平分析得到进一步验证。结果：在结直肠癌细胞系中进行的功能实验表明，转染miR-195-5p模拟物可显著下调KRT80表达，其效果与siRNA直接沉默KRT80的作用相当。两种分子干预方法均能诱导细胞周期G1期阻滞，同时降低G2/M期细胞比例。此外，在结肠炎相关结直肠癌小鼠模型中，体内递送miR-195-5p模拟物可显著降低结肠组织中的Krt80表达。结论：本研究结果表明，miR-195-5p通过负向调控KRT80表达，在结直肠癌中发挥抑癌作用，这一分子机制的揭示为结直肠癌的潜在治疗策略提供了新的理论依据。
miR-195-5p Suppresses KRT80 Expression Inducing Cell Cycle Arrest in Colon Cancer
肿瘤(癌症)患者之家