Wang Zhi, Zhang Yichuan, Zhao Cheng, Li Yangle, Hu Xiheng, Wu Longxiang, Chen Minfeng, Tong Shiyu
Department of Urology Surgery, Xiangya Hospital of Central South University, Changsha 410008, China; Department of Urology, Hunan Children's Hospital, Changsha 410007, China.
Department of Urology Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Cell Signal. 2021 Aug;84:110004. doi: 10.1016/j.cellsig.2021.110004. Epub 2021 Apr 8.
Uncontrolled proliferation and migration of benign prostatic hyperplasia (BPH) epithelial cells play a critical role in the pathogenesis of BPH. The regulatory roles of microRNAs (miRNAs) in multiple human diseases have been observed. This study was dedicated to investigating the regulatory effects of the miR-223-3p on the proliferation and migration of BPH progress. In the present study, the aberrant upregulation of miR-223-3p in BPH samples and BPH-1 cells was determined. TGF-β stimulation induced miR-223-3p expression, promoted BPH-1 cell viability and DNA synthesis, inhibited BPH-1 cell apoptosis, and decreased pro-apoptotic Bax/caspase 3. These changes induced by TGF-β stimulation were further enhanced the overexpression of miR-223-3p and attenuated via the inhibition of miR-223-3p. Under TGF-β stimulation, the overexpression of miR-223-3p enhanced, whereas the inhibition of miR-223-3p inhibited the EMT and MAPK signaling pathways. By targeting the MAP1B 3'UTR, miR-223-3p repressed MAP1B expression. In contrast to miR-223-3p overexpression, MAP1B overexpression attenuated TGF-β-induced changes in BPH-1 cell phenotypes, pro-apoptotic Bax/caspase 3, and the EMT and MAPK signaling pathways; more importantly, MAP1B overexpression significantly attenuated the roles of miR-223-3p overexpression in BPH-1 cell phenotypes, pro-apoptotic Bax/caspase 3, and the EMT and MAPK signaling pathways under TGF-β stimulation. In conclusion, miR-223-3p aggravates the uncontrolled proliferation and migration of BPH-1 cells through targeting MAP1B. The EMT and MAPK signaling pathways might be involved.
良性前列腺增生（BPH）上皮细胞的失控增殖和迁移在BPH的发病机制中起关键作用。已观察到微小RNA（miRNA）在多种人类疾病中的调节作用。本研究致力于探讨miR-223-3p对BPH进展中细胞增殖和迁移的调节作用。在本研究中，测定了BPH样本和BPH-1细胞中miR-223-3p的异常上调。转化生长因子-β（TGF-β）刺激诱导miR-223-3p表达，促进BPH-1细胞活力和DNA合成，抑制BPH-1细胞凋亡，并降低促凋亡蛋白Bax/半胱天冬酶3水平。TGF-β刺激诱导的这些变化在miR-223-3p过表达时进一步增强，而通过抑制miR-223-3p则减弱。在TGF-β刺激下，miR-223-3p过表达增强，而抑制miR-223-3p则抑制上皮-间质转化（EMT）和丝裂原活化蛋白激酶（MAPK）信号通路。通过靶向微管相关蛋白1B（MAP1B）的3'非翻译区（UTR），miR-223-3p抑制MAP1B表达。与miR-223-3p过表达相反，MAP1B过表达减弱了TGF-β诱导的BPH-1细胞表型、促凋亡蛋白Bax/半胱天冬酶3以及EMT和MAPK信号通路的变化；更重要的是，MAP1B过表达显著减弱了TGF-β刺激下miR-223-3p过表达对BPH-1细胞表型、促凋亡蛋白Bax/半胱天冬酶3以及EMT和MAPK信号通路的作用。总之，miR-223-3p通过靶向MAP1B加重BPH-1细胞的失控增殖和迁移。EMT和MAPK信号通路可能参与其中。
