伪基因OCT4-pg5通过与miR-145-5p竞争,上调OCT4B的表达,从而促进膀胱癌的进展。

IF 3.4 3区 生物学 Q3 CELL BIOLOGY Cell Cycle Pub Date : 2024-03-01 Epub Date: 2024-06-06 DOI:10.1080/15384101.2024.2353554
Wuer Zhou, Yue Yang, Wei Wang, Chenglin Yang, Zhi Cao, Xiaoyu Lin, Huifen Zhang, Yuansong Xiao, Xiaoming Zhang
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引用次数: 0

摘要

膀胱癌(BC)是全球最常见的恶性肿瘤之一。竞争性内源性RNA(ceRNA)网络可确定与膀胱癌进展和预后相关的潜在生物标志物。研究发现,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,OCT4-pg5的表达与OCT4B的表达和肿瘤晚期分级相关。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 还通过激活 Wnt/β-catenin 通路、上调基质金属蛋白酶(MMP)2 和 9 以及转录因子锌指 E-box binding homeobox(ZEB)1 和 2 的表达,促进上皮-间质转化(EMT)。OCT4-pg5和OCT4B的高表达可减少细胞凋亡并增加G1期细胞的比例,从而降低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,并增强顺铂抗性。该轴可能是治疗 BC 患者的靶点。
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Pseudogene OCT4-pg5 upregulates OCT4B expression to promote bladder cancer progression by competing with miR-145-5p.

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.

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来源期刊
Cell Cycle
Cell Cycle 生物-细胞生物学
CiteScore
7.70
自引率
2.30%
发文量
281
审稿时长
1 months
期刊介绍: Cell Cycle is a bi-weekly peer-reviewed journal of high priority research from all areas of cell biology. Cell Cycle covers all topics from yeast to man, from DNA to function, from development to aging, from stem cells to cell senescence, from metabolism to cell death, from cancer to neurobiology, from molecular biology to therapeutics. Our goal is fast publication of outstanding research.
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