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miR-1272-ADAM9-CDCP1 信号通路在胶质瘤进展中的新兴作用。

The emerging role of the MiR-1272-ADAM9-CDCP1 signaling pathway in the progression of glioma.

机构信息

Department of Physiology, Zunyi Medical University, Zunyi, China.

Department of Pathophysiology, Zunyi Medical University, Zunyi, China.

出版信息

Aging (Albany NY). 2020 Nov 26;13(1):894-909. doi: 10.18632/aging.202196.

Abstract

Glioma is a primary, malignant, and aggressive brain tumor in adults. To develop new therapeutic strategies for glioma, we must determine its underlying mechanisms. In the present study, we aimed to investigate the potential role of miR-1272-ADAM9-CDCP1 signaling in the progression of glioma. We found that ectopic expression of miR-1272 produced significant inhibitory effects on cell proliferation and migration and was associated with cell cycle G0/G1 arrest in A172 and SHG44 glioma cells. Using the luciferase reporter assay, we identified ADAM9 as a target of miR-1272. The expression of ADAM9 was markedly decreased or increased after overexpression or inhibition, respectively, of miR-1272 in glioma cells. Moreover, overexpression of ADAM9 reversed the inhibitory effects of miR-1272 on glioma cell progression. Furthermore, CDCP1 served as a potential downstream molecule of miR-1272/ADAM9 signaling in glioma and promoted the proliferation and migration of glioma. Results derived from clinical samples and online databases confirmed correlations between the expression of ADAM9 and CDCP1 and both the severity and prognosis of glioma. In conclusion, these results suggest that miR-1272 and CDCP1 may act as novel regulators in glioma. The miR-1272/ADAM9/CDCP1 pathway may serve as a potential candidate pathway for the prevention of glioma.

摘要

胶质母细胞瘤是成人原发性、恶性、侵袭性脑肿瘤。为了开发胶质母细胞瘤的新治疗策略,我们必须确定其潜在的机制。在本研究中,我们旨在研究 miR-1272-ADAM9-CDCP1 信号在胶质母细胞瘤进展中的潜在作用。我们发现,miR-1272 的异位表达对 A172 和 SHG44 神经胶质瘤细胞的增殖和迁移有显著的抑制作用,并与细胞周期 G0/G1 期阻滞有关。通过荧光素酶报告基因检测,我们确定 ADAM9 是 miR-1272 的靶基因。miR-1272 在神经胶质瘤细胞中过表达或抑制后,ADAM9 的表达明显降低或升高。此外,ADAM9 的过表达逆转了 miR-1272 对神经胶质瘤细胞进展的抑制作用。此外,CDCP1 作为 miR-1272/ADAM9 信号在神经胶质瘤中的潜在下游分子,促进了神经胶质瘤的增殖和迁移。来自临床样本和在线数据库的结果证实了 ADAM9 和 CDCP1 的表达与胶质母细胞瘤的严重程度和预后之间的相关性。总之,这些结果表明,miR-1272 和 CDCP1 可能是胶质母细胞瘤的新型调节因子。miR-1272/ADAM9/CDCP1 通路可能是预防胶质母细胞瘤的潜在候选途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c889/7835014/0fb4909975bf/aging-13-202196-g001.jpg

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