Armstrong Lee, Willoughby Colin E, McKenna Declan J
Genomic Medicine Research Group, Ulster University, Cromore Road, Coleraine BT52 1SA, UK.
Cells. 2023 Sep 5;12(18):2207. doi: 10.3390/cells12182207.
An altered expression of miR-143-3p has been previously reported in prostate cancer where it is purported to play a tumor suppressor role. Evidence from other cancers suggests miR-143-3p acts as an inhibitor of epithelial-to-mesenchymal transition (EMT), a key biological process required for metastasis. However, in prostate cancer the interaction between miR-143-3p and EMT-associated mechanisms remains unclear. Therefore, this paper investigated the link between miR-143-3p and EMT in prostate cancer using in vitro and in silico analyses. PCR detected that miR-143-3p expression was significantly decreased in prostate cancer cell lines compared to normal prostate cells. Bioinformatic analysis of The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) data showed a significant downregulation of miR-143-3p in prostate cancer, correlating with pathological markers of advanced disease. Functional enrichment analysis confirmed the significant association of miR-143-3p and its target genes with EMT. The EMT-linked gene AKT1 was subsequently shown to be a novel target of miR-143-3p in prostate cancer cells. The in vitro manipulation of miR-143-3p levels significantly altered the cell proliferation, clonogenicity, migration and expression of EMT-associated markers. Further TCGA PRAD analysis suggested miR-143-3p tumor expression may be a useful predictor of disease recurrence. In summary, this is the first study to report that miR-143-3p overexpression in prostate cancer may inhibit EMT by targeting AKT1. The findings suggest miR-143-3p could be a useful diagnostic and prognostic biomarker for prostate cancer.
先前有报道称，miR - 143 - 3p在前列腺癌中表达发生改变，据称它发挥着肿瘤抑制作用。来自其他癌症的证据表明，miR - 143 - 3p可作为上皮 - 间质转化（EMT）的抑制剂，而EMT是转移所需的关键生物学过程。然而，在前列腺癌中，miR - 143 - 3p与EMT相关机制之间的相互作用仍不清楚。因此，本文通过体外和计算机分析研究了前列腺癌中miR - 143 - 3p与EMT之间的联系。PCR检测发现，与正常前列腺细胞相比，前列腺癌细胞系中miR - 143 - 3p表达显著降低。对癌症基因组图谱前列腺腺癌（TCGA PRAD）数据的生物信息学分析显示，前列腺癌中miR - 143 - 3p显著下调，与晚期疾病的病理标志物相关。功能富集分析证实了miR - 143 - 3p及其靶基因与EMT的显著关联。随后发现，与EMT相关的基因AKT1是前列腺癌细胞中miR - 143 - 3p的新靶标。体外对miR - 143 - 3p水平的调控显著改变了细胞增殖、克隆形成能力、迁移以及EMT相关标志物的表达。进一步的TCGA PRAD分析表明，miR - 143 - 3p在肿瘤中的表达可能是疾病复发的有用预测指标。总之，这是第一项报道前列腺癌中miR - 143 - 3p过表达可能通过靶向AKT1抑制EMT的研究。这些发现表明，miR - 143 - 3p可能是前列腺癌有用的诊断和预后生物标志物。
