Department of Medical Sciences, University of Ferrara, 64/b, Fossato di Mortara Street, 44121, Ferrara, Italy.
Center for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 44121, Ferrara, Italy.
Sci Rep. 2023 Dec 18;13(1):22872. doi: 10.1038/s41598-023-49837-0.
Intercellular adhesion is a key function for epithelial cells. The fundamental mechanisms relying on epithelial cell adhesion have been partially uncovered. Hsa-microRNA-1249-3p (hsa-miR-1249-3p) plays a role in the epithelial mesenchymal transition in carcinoma cells, but its physiological function in epithelial cells is unknown. We aimed to investigate the role and molecular mechanisms of hsa-miR-1249-3p on epithelial cell functions. Hsa-miR-1249-3p was overexpressed in human epithelial cells and uterine cervical tissues, compared to cervical carcinoma cells and precancerous tissues, respectively. Hsa-miR-1249-3p was analyzed to verify its regulatory function on Homeobox A13 (HOXA13) target gene and its downstream cell adhesion gene β-catenin. Functional experiments indicated that hsa-miR-1249-3p inhibition prompted the mRNA and protein overexpression of HOXA13 which, in turn, led to the β-catenin protein expression. Moreover, hsa-miR-1249-3p inhibition induced a strong colony forming ability in epithelial cells, suggesting the miR involvement in cell adhesion machinery. These data indicate that hsa-miR-1249-3p regulates the expression of HOXA13 and its downstream cell adhesion gene β-catenin, possible resulting in cell adhesion modification in epithelial cells. This study will allow the set-up of further investigations aimed at exploring the relationship between the hsa-miR-1249-3p/HOXA13 axis and downstream cell adhesion genes.
细胞间黏附是上皮细胞的关键功能。依赖于上皮细胞黏附的基本机制已部分被揭示。Hsa-microRNA-1249-3p(hsa-miR-1249-3p)在癌细胞的上皮间质转化中发挥作用,但它在上皮细胞中的生理功能尚不清楚。我们旨在研究 hsa-miR-1249-3p 在上皮细胞功能中的作用和分子机制。与宫颈癌细胞和癌前组织相比,hsa-miR-1249-3p 在人上皮细胞和子宫颈组织中过表达。分析 hsa-miR-1249-3p 以验证其对同源盒 A13(HOXA13)靶基因及其下游细胞黏附基因β-连环蛋白的调节功能。功能实验表明,hsa-miR-1249-3p 抑制促进了 HOXA13 的 mRNA 和蛋白过表达,进而导致β-连环蛋白蛋白的表达。此外,hsa-miR-1249-3p 抑制诱导上皮细胞中强烈的集落形成能力,表明 miR 参与细胞黏附机制。这些数据表明,hsa-miR-1249-3p 调节 HOXA13 的表达及其下游细胞黏附基因β-连环蛋白,可能导致上皮细胞黏附修饰。本研究将进一步探讨 hsa-miR-1249-3p/HOXA13 轴与下游细胞黏附基因之间的关系。