Wang Linjun, Fang Xin, Dong Yangmin, Wang Songmao, Pan Jun, Wu Ziheng, Qiu Chenyang
Department of Vascular Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Vascular Surgery, Hangzhou Third People's Hospital, Hangzhou, China.
Arch Med Sci. 2023 Aug 17;21(3):930-943. doi: 10.5114/aoms/171024. eCollection 2025.
Data from the CEO database show that microRNA (miR)-28-3p levels are elevated in diabetic patients. Nevertheless, the role of miR-28-3p in peripheral artery disease with diabetes has not been investigated.
The levels of miR-28-3p, CXXC5, CXXC-type zinc finger protein 5, and CXXC5's downstream molecules as well as endothelial function were investigated. Dual luciferase analyses were used to confirm the binding site of miR-28-3p and CXXC5.
Under high-glucose conditions, miR-28-3p expression is upregulated, whereas CXXC5 expression is downregulated. Overexpression of miR-28-3p increased cell apoptosis and inhibited cell proliferation, migration, and vessel formation, whilst inhibiting its expression had the opposite effect. The overexpression and inhibition of miR-28-3p could also influence both the mRNA and protein levels of CXXC5 and its known downstream molecules. Analysis of bioinformatics data revealed a potential binding site for miR-28-3p and CXXC5. Dual luciferase analyses demonstrated that miR-28-3p suppressed CXXC5 expression by targeting the 3'-untranslated region (3'-UTR) of CXXC5. Following that, we overexpressed both miR-28-3p and CXXC5. The level of CXXC5 and its known downstream signaling molecules decreased with miR-28-3p overexpression alone. As anticipated, co-overexpression of miR-28-3p and CXXC5 partially reversed the effect of miR-28-3p mimics.
These findings indicated that miR-28-3p regulated high glucose-induced endothelial dysfunction by targeting CXXC5.
首席执行官数据库的数据显示，糖尿病患者体内微小RNA（miR）-28-3p水平升高。然而，miR-28-3p在糖尿病外周动脉疾病中的作用尚未得到研究。
研究了miR-28-3p、CXXC5（CXXC型锌指蛋白5）、CXXC5的下游分子水平以及内皮功能。采用双荧光素酶分析来确认miR-28-3p与CXXC5的结合位点。
在高糖条件下，miR-28-3p表达上调，而CXXC5表达下调。miR-28-3p过表达增加细胞凋亡，抑制细胞增殖、迁移和血管形成，而抑制其表达则产生相反的效果。miR-28-3p的过表达和抑制也会影响CXXC5及其已知下游分子的mRNA和蛋白质水平。生物信息学数据分析揭示了miR-28-3p与CXXC5之间的潜在结合位点。双荧光素酶分析表明，miR-28-3p通过靶向CXXC5的3'非翻译区（3'-UTR）抑制CXXC5表达。随后，我们同时过表达了miR-28-3p和CXXC5。单独miR-28-3p过表达时，CXXC5及其已知下游信号分子的水平降低。正如预期的那样，miR-28-3p和CXXC5的共过表达部分逆转了miR-28-3p模拟物的作用。
这些发现表明，miR-28-3p通过靶向CXXC5调节高糖诱导的内皮功能障碍。
