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microRNA-211-mediated targeting of the INHBA-TGF-β axis suppresses prostate tumor formation and growth
Cancer Gene Therapy ( IF 4.8 ) Pub Date : 2020-11-22 , DOI: 10.1038/s41417-020-00237-w
Zhifeng Zhao 1 , Kai Wang 1 , Shanfeng Tan 1
Affiliation  

Prostate cancer (PCa) stem cells increase the sustainability of tumor growth, resulting in high relapse rates in patients with PCa. This goal of the present study was to elucidate the function of microRNA (miR)-211 in PCa stem cell activities. Based on the initial findings from the GSE26910 dataset, inhibin-β A (INHBA) was used for subsequent experiments, and miR-211 was then predicted as a candidate regulatory miR. Subsequently, INHBA and miR-211 were observed to be highly and poorly expressed in PCa tissues, respectively, and miR-211 negatively target INHBA. CD44+CD133+ cells were isolated, and both miR-211 and INHBA expression was altered in these cells to assess functional role of miR-211 and INHBA in PCa stem cells. Overexpression of miR-211 decreased expression of TGF-β1, TGF-β2, smad2, smad3, phosphorylated smad2 and smad3, and stem cell markers. miR-211 upregulation or INHBA knockdown resulted in reductions in the proliferation, invasion, colony-forming ability, sphere-forming ability, and stemness of PCa stem cells but enhanced their apoptosis in vitro. Furthermore, miR-211 upregulation or INHBA silencing decreased tumor growth and cell apoptosis in vivo. Taken together, these results indicate that upregulation of miR-211 has tumor-suppressive properties by inhibiting TGF-β pathway activation via INHBA in PCa stem cells.



中文翻译:

microRNA-211 介导的 INHBA-TGF-β 轴靶向抑制前列腺肿瘤的形成和生长

前列腺癌 (PCa) 干细胞增加了肿瘤生长的可持续性,导致 PCa 患者的高复发率。本研究的目的是阐明 microRNA (miR)-211 在 PCa 干细胞活动中的功能。基于 GSE26910 数据集的初步发现,抑制素-β A (INHBA) 用于后续实验,然后预测 miR-211 作为候选调节 miR。随后,观察到 INHBA 和 miR-211 分别在 PCa 组织中高表达和低表达,并且 miR-211 负向靶向 INHBA。CD44 + CD133 +分离细胞,并改变这些细胞中的 miR-211 和 INHBA 表达,以评估 miR-211 和 INHBA 在 PCa 干细胞中的功能作用。miR-211 的过表达降低了 TGF-β1、TGF-β2、smad2、smad3、磷酸化 smad2 和 smad3 以及干细胞标志物的表达。miR-211 上调或 INHBA 敲低导致 PCa 干细胞的增殖、侵袭、集落形成能力、球形成能力和干性降低,但在体外增强了它们的细胞凋亡。此外,miR-211 上调或 INHBA 沉默降低了体内肿瘤生长和细胞凋亡。总之,这些结果表明 miR-211 的上调通过在 PCa 干细胞中通过 INHBA 抑制 TGF-β 通路激活而具有肿瘤抑制特性。

更新日期:2020-11-22
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