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假基因 OCT4-pg5 通过与 miR-145-5p 竞争上调 OCT4B 的表达来促进膀胱癌的进展。

Pseudogene OCT4-pg5 upregulates OCT4B expression to promote bladder cancer progression by competing with miR-145-5p.

机构信息

The Department of Urology, General Hospital of Southern Theater Command, PLA, Guangzhou, China.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.

出版信息

Cell Cycle. 2024 Mar;23(6):645-661. doi: 10.1080/15384101.2024.2353554. Epub 2024 Jun 6.

Abstract

Bladder cancer (BC) is one of the most common malignant neoplasms worldwide. Competing endogenous RNA (ceRNA) networks may identify potential biomarkers associated with the progression and prognosis of BC. The OCT4-pg5/miR-145-5p/OCT4B ceRNA network was found to be related to the progression and prognosis of BC. OCT4-pg5 expression was significantly higher in BC cell lines than in normal bladder cells, with OCT4-pg5 expression correlating with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, whereas miR-145-5p suppressed these activities. The 3' untranslated region (3'UTR) of OCT4-pg5 competed for miR-145-5p, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted epithelial-mesenchymal transition (EMT) by activating the Wnt/β-catenin pathway and upregulating the expression of matrix metalloproteinases (MMPs) 2 and 9 as well as the transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. The OCT4-pg5/miR-145-5p/OCT4B axis promotes the progression of BC by inducing EMT via the Wnt/β-catenin pathway and enhances cisplatin resistance. This axis may represent a therapeutic target in patients with BC.

摘要

膀胱癌 (BC) 是全球最常见的恶性肿瘤之一。竞争内源性 RNA (ceRNA) 网络可能会确定与 BC 进展和预后相关的潜在生物标志物。OCT4-pg5/miR-145-5p/OCT4B ceRNA 网络与 BC 的进展和预后有关。OCT4-pg5 在 BC 细胞系中的表达明显高于正常膀胱细胞,并且 OCT4-pg5 的表达与 OCT4B 的表达和晚期肿瘤分级相关。OCT4-pg5 和 OCT4B 的过表达促进了 BC 细胞的增殖和侵袭,而 miR-145-5p 则抑制了这些活性。OCT4-pg5 的 3'非翻译区 (3'UTR) 与 miR-145-5p 竞争,从而增加了 OCT4B 的表达。此外,OCT4-pg5 通过激活 Wnt/β-catenin 通路并上调基质金属蛋白酶 (MMP)2 和 9 以及转录因子锌指 E 盒结合同源盒 (ZEB)1 和 2 的表达来促进上皮间质转化 (EMT)。OCT4-pg5 和 OCT4B 的高表达通过减少细胞凋亡和增加 G1 期细胞比例来降低 BC 细胞对顺铂的敏感性。OCT4-pg5/miR-145-5p/OCT4B 轴通过 Wnt/β-catenin 通路诱导 EMT 促进 BC 的进展,并增强顺铂耐药性。该轴可能代表 BC 患者的治疗靶点。

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