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长链非编码 RNA HOXD-AS1 的敲低通过海绵吸附 miR-204 抑制胶质瘤细胞的增殖、迁移和侵袭并增强顺铂敏感性。

Knockdown of lncRNA HOXD-AS1 suppresses proliferation, migration and invasion and enhances cisplatin sensitivity of glioma cells by sponging miR-204.

机构信息

Department of neurosurgery, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510000, China.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510000, China.

出版信息

Biomed Pharmacother. 2019 Apr;112:108633. doi: 10.1016/j.biopha.2019.108633. Epub 2019 Feb 20.

Abstract

Increasing evidence suggests the involvement of long noncoding RNAs (lncRNAs) in various biological process including cancer progression and drug resistance. LncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) had been demonstrated to act as an oncogenic gene, contributing to the development and progression of several cancers. However, its functional role and molecular mechanism underlying glioma progression and cisplatin (DDP) resistance has not been well elucidated. In this study, we found that HOXD-AS1 was up-regulated in glioma tissues and cells and negatively correlated with survival time. HOXD-AS1 knockdown suppressed proliferation, migration and invasion as well as enhanced DDP sensitivity of glioma cells. Moreover, HOXD-AS1 could function as a miR-204 sponge in glioma cells. Overexpression of miR-204 could mimic the functional role of down-regulated HOXD-AS1 in glioma cells. Furthermore, miR-204 inhibition reversed the effect of HOXD-AS1 knockdown on cancer progression and DDP sensitivity of glioma cells. In conclusion, knockdown of HOXD-AS1 suppressed proliferation, migration and invasion and enhanced DDP sensitivity of glioma cells through sequestering miR-204, providing a promising therapeutic target for glioma patients.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)参与了多种生物学过程,包括癌症的进展和耐药性。lncRNA HOXD 簇反义 RNA 1(HOXD-AS1)已被证明是一种致癌基因,促进了几种癌症的发展和进展。然而,其在胶质瘤进展和顺铂(DDP)耐药性中的功能作用和分子机制尚不清楚。在本研究中,我们发现 HOXD-AS1 在胶质瘤组织和细胞中上调,与生存时间呈负相关。HOXD-AS1 敲低抑制了胶质瘤细胞的增殖、迁移和侵袭,并增强了 DDP 敏感性。此外,HOXD-AS1 可以作为胶质瘤细胞中的 miR-204 海绵。miR-204 的过表达可以模拟下调 HOXD-AS1 在胶质瘤细胞中的功能作用。此外,HOXD-AS1 敲低对胶质瘤细胞的癌症进展和 DDP 敏感性的影响可以被 miR-204 抑制所逆转。总之,下调 HOXD-AS1 通过结合 miR-204 抑制了胶质瘤细胞的增殖、迁移和侵袭,并增强了 DDP 敏感性,为胶质瘤患者提供了有前途的治疗靶点。

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