Inhibition of miR-29a-3p Alleviates Apoptosis of Lens Epithelial Cells via Upregulation of CAND1

Accumulated evidence has shown that microRNAs (miRNAs) are closely related to the pathogenesis and progression of senile cataracts. Here we investigate the effect of miR-29a-3p in cataractogenesis and determined the potential molecular mechanism involved. In this study, we constructed a selenite cataract model in rats and obtained the miRNAs related to cataracts by whole transcriptome sequencing. To investigate the effect and mechanism of miR-29a-3p on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, luciferase reporter assay, Edu assay, and western blot analysis. Sequencing data showed downregulation of miR-29a-3p in rats with selenite cataracts. Down-regulation of miR-29a-3p could promote lens epithelial cells (SRA01/04) proliferation and inhibit cell apoptosis, and miR-29a-3p silence could inhibit the development of cataracts. Additionally, CAND1 was a direct target gene for miR-29a-3p. These data demonstrate that miR-29a-3p inhibits apoptosis of lens epithelial cells by regulating CAND1, which may be a potential target for senile cataracts.

越来越多的研究证据表明，微小RNA（microRNAs，miRNAs）与老年性白内障的发病机制及病情进展密切相关。本研究旨在探讨miR-29a-3p在白内障发生中的作用，并阐明其潜在的分子机制。本研究通过构建亚硒酸盐诱导的大鼠白内障模型，利用全转录组测序技术筛选得到与白内障相关的微小RNA。为探究miR-29a-3p对白内障的作用及其分子机制，本研究开展了多项体内及体外实验，包括CCK-8检测、流式细胞术、荧光素酶报告基因实验、Edu检测及蛋白质印迹分析。测序结果显示，在亚硒酸盐诱导的白内障大鼠模型中，miR-29a-3p的表达显著下调。miR-29a-3p的下调可促进晶状体上皮细胞（SRA01/04）的增殖并抑制细胞凋亡，而miR-29a-3p的基因沉默则可延缓白内障的进展。此外，CAND1是miR-29a-3p的直接靶基因。本研究数据表明，miR-29a-3p通过调控CAND1抑制晶状体上皮细胞的凋亡，这一机制或可成为老年性白内障的潜在治疗靶点。