UBDP1 pseudogene and UBD network competitively bind miR‑6072 to promote glioma progression

UBDP1 假基因和 UBD 网络竞争性结合 miR-6072 促进神经胶质瘤进展

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作者:Fan Hong #, Zhenyu Gong #, Chao Chen #, Tianzhen Hua, Qilin Huang, Yu'e Liu, Peipei Ma, Xu Zhang, Hongxiang Wang, Juxiang Chen

Abstract

Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain enigmatic. In the present study, a novel pseudogene was identified, UBDP1, which is significantly upregulated in glioblastoma and positively correlated with the expression of its parent gene, UBD. Additionally, high levels of these paired genes are linked with a poor prognosis for patients. In the present study, clinical samples were collected followed by various analyses including microarray for long non‑coding RNAs, reverse transcription‑quantitative PCR, fluorescence in situ hybridization and western blotting. Cell lines were authenticated and cultured then subjected to various assays for proliferation, migration, and invasion to investigate the molecular mechanisms. Bioinformatic tools identified miRNA targets, and luciferase reporter assays validated these interactions. A tumor xenograft model in mice was used for in vivo studies. In vitro and in vivo studies have demonstrated that UBDP1, localized in the cytoplasm, functions as a tumor‑promoting factor influencing cell proliferation, migration, invasion and tumor growth. Mechanistic investigations have indicated that UBDP1 exerts its oncogenic effects by decoying miR‑6072 from UBD mRNA, thus forming a competitive endogenous RNA network, which results in the enhanced oncogenic activity of UBD. The present findings offered new insights into the role of pseudogenes in glioma progression, suggesting that targeting the UBDP1/miR‑6072/UBD network may serve as a potential therapeutic strategy for glioma patients.

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