Department of Neurosurgery, The Huangdao District People's Hospital, No. 287 Renmin Road, Qingdao, 266400, Shandong, China.
Department of Neurosurgery, The Huangdao District Second People's Hospital, Qingdao, Shandong, China.
Neurochem Res. 2020 Dec;45(12):2894-2902. doi: 10.1007/s11064-020-03138-4. Epub 2020 Sep 29.
Glioblastoma is one of the most frequent and aggressive primary tumor of glial brain tumors. Long non-coding RNA Prostate cancer-associated ncRNA transcript 6 (PCAT6) has been identified to influence the progression of many cancers, but its expression and functions in glioblastoma remain unclear. In this study, we intended to investigate the expression, functions and the corresponding mechanisms of PCAT6 in glioblastoma. We observed that PCAT6 expression was upregulated in glioblastoma tissues and cell lines and its high expression was due to the transcriptional activation by Yin Yang 1. miR-513 was a target of PCAT6 and Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was a target of miR-513. Hence, PCAT6 upregulated IGF2BP1 expression via miR-513 in a competing endogenous RNAs manner. PCAT6 and IGF2BP1 functioned as oncogenes while miR-513 acted as a tumor suppressor gene in glioblastoma. PCAT6 and miR-513 modulated the proliferation and survival of glioblastoma cells via AKT signaling by mediating IGF2BP1. IGF2BP1 raised the expression of PCAT6 by increasing its stability. In conclusion, our results indicate that PCAT6/miR-513/IGF2BP1 positive feedback loop plays a crucial role in facilitating glioblastoma progression.
胶质母细胞瘤是最常见和侵袭性最强的神经胶质瘤。长链非编码 RNA 前列腺癌相关 ncRNA 转录本 6(PCAT6)已被证实影响许多癌症的进展,但它在胶质母细胞瘤中的表达和功能仍不清楚。在这项研究中,我们旨在研究 PCAT6 在胶质母细胞瘤中的表达、功能及其相应的机制。我们观察到 PCAT6 在胶质母细胞瘤组织和细胞系中表达上调,其高表达是由于 Yin Yang 1 的转录激活。miR-513 是 PCAT6 的靶标,胰岛素样生长因子 2 mRNA 结合蛋白 1(IGF2BP1)是 miR-513 的靶标。因此,PCAT6 通过 miR-513 以竞争性内源性 RNA 的方式上调 IGF2BP1 的表达。PCAT6 和 IGF2BP1 在胶质母细胞瘤中作为癌基因,而 miR-513 作为肿瘤抑制基因发挥作用。PCAT6 和 miR-513 通过调节 IGF2BP1 来调节 AKT 信号通路,从而影响胶质母细胞瘤细胞的增殖和存活。IGF2BP1 通过增加其稳定性来提高 PCAT6 的表达。总之,我们的结果表明,PCAT6/miR-513/IGF2BP1 正反馈环在促进胶质母细胞瘤进展中起着关键作用。