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长链非编码 RNA GAS5 通过 miR-18a-5p/AXIN2/GSK3β 轴调控 Wnt/β-catenin 通路抑制膀胱癌细胞的增殖和迁移。

LncRNA GAS5 regulates the Wnt/β-catenin pathway through the miR-18a-5p/AXIN2/GSK3β axis to inhibit the proliferation and migration of bladder cancer cells.

机构信息

Department of Urology, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, P. R. China.

Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, 241000, China.

出版信息

Carcinogenesis. 2022 Dec 31;43(12):1176-1189. doi: 10.1093/carcin/bgac087.

DOI:10.1093/carcin/bgac087
PMID:36331809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10122427/
Abstract

LncRNA growth arrest specific 5 (GAS5) has been confirmed to play an essential role in a number of biological processes, such as tumor regulation and gene transcription. GAS5 has been shown to be a tumor suppressor gene in many types of cancer, but its specific mechanism of action in bladder cancer (BC) remains to be elucidated. In this study, we explored the biological properties of GAS5 in BC and its mechanism of action in BC. We analyzed the expression of GAS5 in 50 pairs of BC tissues and found that GAS5 was low expressed in BC tissues compared with normal mucosal tissues. In vitro and in vivo experiments showed that GAS5 could affect the proliferation and migration of BC cells. Nucleoplasmic isolation assays and fluorescence in situ hybridization (FISH) assays demonstrated the localization of GAS5 in cell cytoplasm. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP) and luciferase assay demonstrated the target binding relationship of GAS5 with miR-18a-5p. Rescue experiments demonstrated that GAS5 promoted the proliferation and migration of BC cells through target binding of miR-18a-5p. Moreover, miR-18a-5p bound to its targets AXIN2 and GSK3β, which in turn affected the expression of Wnt/β-catenin pathway-related proteins. Our findings demonstrate that GAS5 regulates Wnt/β-catenin pathway activity by regulating the miR-18a-5p/AXIN2/GSK3β axis to modulate BC progression, providing a new potential therapeutic strategy for the treatment of BC.

摘要

长链非编码 RNA 生长停滞特异性 5(GAS5)已被证实在许多生物过程中发挥着重要作用,如肿瘤调控和基因转录。GAS5 已被证明是许多类型癌症的肿瘤抑制基因,但它在膀胱癌(BC)中的具体作用机制仍有待阐明。在本研究中,我们探讨了 GAS5 在 BC 中的生物学特性及其在 BC 中的作用机制。我们分析了 50 对 BC 组织中 GAS5 的表达情况,发现 GAS5 在 BC 组织中的表达低于正常黏膜组织。体外和体内实验表明,GAS5 可影响 BC 细胞的增殖和迁移。核质分离实验和荧光原位杂交(FISH)实验证实了 GAS5 在细胞质中的定位。RNA 免疫沉淀(RIP)和荧光素酶报告基因实验证实了 GAS5 与 miR-18a-5p 的靶结合关系。挽救实验表明,GAS5 通过与 miR-18a-5p 的靶结合促进 BC 细胞的增殖和迁移。此外,miR-18a-5p 与靶基因 AXIN2 和 GSK3β 结合,进而影响 Wnt/β-catenin 通路相关蛋白的表达。我们的研究结果表明,GAS5 通过调节 miR-18a-5p/AXIN2/GSK3β 轴调节 Wnt/β-catenin 通路活性,从而调节 BC 的进展,为 BC 的治疗提供了一种新的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/19b60713e6e3/bgac087_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/20db6897c01c/bgac087_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/a2c8eb821245/bgac087_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/16c7297f42ea/bgac087_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/668bc94fff76/bgac087_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/2e000a2a87c5/bgac087_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/5b875ba42da2/bgac087_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/19b60713e6e3/bgac087_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/20db6897c01c/bgac087_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/a2c8eb821245/bgac087_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/16c7297f42ea/bgac087_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/668bc94fff76/bgac087_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/2e000a2a87c5/bgac087_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/5b875ba42da2/bgac087_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/10122427/19b60713e6e3/bgac087_fig6.jpg

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