Department of Oncology, the First Affiliated Hospital of Wannan Medical College, Wuhu 241002, China.
Department of Thyroid and Breast, the Second Affiliated Hospital of Wannan Medical College, Wuhu 241002, China.
Acta Biochim Biophys Sin (Shanghai). 2023 Dec 25;55(12):1892-1901. doi: 10.3724/abbs.2023226.
Krüppel-like zinc-finger transcription factor 5 (KLF5) is a vital regulator of breast cancer (BC) onset and progression. The mechanism by which KLF5 regulates BC is still not clearly known. In this study, bioinformatics analysis shows that BC-affected individuals with elevated KLF5 expression levels have poor clinical outcomes. We further verify that miR-145-5p regulated KLF5 expression to promote cell apoptosis and inhibit cell proliferation in BC via dual-luciferase reporter assay, western blot analysis, qRT-PCR, CCK-8 assay and cell apoptosis assay. In addition, based on bioinformatics analysis, the binding of ENST00000422059 with miR-145-5p is confirmed by dual-luciferase reporter assay. Subsequently, FISH, western blot analysis, qRT-PCR, CCK-8 and cell apoptosis assays verified that ENST00000422059 increases KLF5 protein expression by sponging miRNA to promote cell proliferation and inhibit cell apoptosis. Finally, ENST00000422059 is found to accelerate tumor progression by regulating the miR-145-5p/KLF5 axis . In conclusion, this study suggests that ENST00000422059 upregulates KLF5 by sponging miR-145-5p to promote BC progression.
Krüppel 样锌指转录因子 5(KLF5)是乳腺癌(BC)发生和进展的重要调节因子。KLF5 调节 BC 的机制尚不清楚。在这项研究中,生物信息学分析表明,KLF5 表达水平升高的 BC 患者临床结局较差。我们进一步验证了 miR-145-5p 通过双荧光素酶报告基因检测、western blot 分析、qRT-PCR、CCK-8 检测和细胞凋亡检测来调节 KLF5 表达,从而促进 BC 细胞凋亡和抑制细胞增殖。此外,基于生物信息学分析,通过双荧光素酶报告基因检测证实了 ENST00000422059 与 miR-145-5p 的结合。随后,通过 FISH、western blot 分析、qRT-PCR、CCK-8 和细胞凋亡检测验证了 ENST00000422059 通过海绵 miRNA 增加 KLF5 蛋白表达,从而促进细胞增殖和抑制细胞凋亡。最后,发现 ENST00000422059 通过调节 miR-145-5p/KLF5 轴加速肿瘤进展。综上所述,本研究表明,ENST00000422059 通过海绵 miR-145-5p 上调 KLF5 促进 BC 进展。