Department of Neurosurgery, Xiangya Hospital, The Central South University (CSU), Changsha, 410008, PR China; Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, PR China.
Department of Neurosurgery, Xiangya Hospital, The Central South University (CSU), Changsha, 410008, PR China.
Exp Cell Res. 2021 May 1;402(1):112547. doi: 10.1016/j.yexcr.2021.112547. Epub 2021 Mar 12.
The high aggressiveness of gliomas remains a huge challenge to clinical therapies, and the hypoxic microenvironment in the core region is a critical contributor to glioma aggressiveness. In this study, it was found that miR-485-5p was low expressed within glioma tissue samples and cells. GO enrichment annotation indicated that the predicted downstream targets miR-485-5p were enriched in hypoxia response and decreased oxygen level. In glioma cells, miR-485-5p overexpression suppressed cell viability, migratory ability, and invasive ability under both normoxic and hypoxic conditions. Through direct binding, miR-485-5p suppressed SRPK1 expression. Under hypoxia, SRPK1 overexpression enhanced hypoxia-induced glioma cell aggressiveness and significantly reversed the effects of miR-485-5p overexpression. Moreover, HIF1A could target the miR-485-5p promoter region to inhibit the transcription. HIF1A, miR-485-5p, and SRPK1 form a regulatory axis, which modulates glioma cell aggressiveness under hypoxia. In conclusion, we identify a HIF1A/miR-485-5p/SRPK1 axis that modulates the aggressiveness of glioma cells under hypoxia. The axis could potentially provide new research avenues in the treatment of gliomas considering the hypoxic environment in its core.
神经胶质瘤的高度侵袭性仍然是临床治疗的巨大挑战，而核心区域的缺氧微环境是促进神经胶质瘤侵袭性的关键因素。在这项研究中，研究人员发现 miR-485-5p 在神经胶质瘤组织样本和细胞中低表达。GO 富集注释表明，miR-485-5p 的预测下游靶标在缺氧反应和氧水平降低中富集。在神经胶质瘤细胞中，miR-485-5p 的过表达在常氧和缺氧条件下均抑制细胞活力、迁移能力和侵袭能力。通过直接结合，miR-485-5p 抑制 SRPK1 的表达。在缺氧条件下，SRPK1 的过表达增强了缺氧诱导的神经胶质瘤细胞侵袭性，并显著逆转了 miR-485-5p 过表达的作用。此外，HIF1A 可以靶向 miR-485-5p 启动子区域抑制转录。HIF1A、miR-485-5p 和 SRPK1 形成一个调节轴，在缺氧条件下调节神经胶质瘤细胞的侵袭性。总之，我们确定了一个 HIF1A/miR-485-5p/SRPK1 轴，该轴调节缺氧条件下神经胶质瘤细胞的侵袭性。鉴于核心区域的缺氧环境，该轴可能为神经胶质瘤的治疗提供新的研究途径。
