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SNHG17 通过靶向 miR-876-5p/ERLIN2 轴驱动星形细胞瘤的恶性行为。

SNHG17 drives malignant behaviors in astrocytoma by targeting miR-876-5p/ERLIN2 axis.

机构信息

Department of Neurology, the Second Hospital of Heibei Medical University, No. 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.

出版信息

BMC Cancer. 2020 Sep 3;20(1):839. doi: 10.1186/s12885-020-07280-8.

Abstract

BACKGROUND

Astrocytoma is a common tumor type in primary central nervous system and has a high death rate around the world. Aberrant expression of long non-coding RNAs (lncRNAs) has been introduced by emerging studies to result in the development of diverse cancers.

METHODS

RT-qPCR examined the expression of SNHG17, miR-876-5p and ERLIN2, and western blot evaluated ERLIN2 protein level. RNA pull down and luciferase reporter assays illustrated the relationships between SNHG17 and its downstream molecules.

RESULTS

SNHG17 was up-regulated in astrocytoma cells. Moreover, SNHG17 silence could repress the proliferation, migration and invasion of astrocytoma cells. Besides, miR-876-5p was selected out as a downstream molecule of SNHG17 in astrocytoma. ERLIN2 was determined to be targeted by miR-876-5p. ERLIN2 mRNA and protein levels were lessened by miR-876-5p overexpression and SNHG17 silence. Additionally, miR-876-5p overexpression decelerated the biological processes of astrocytoma cells, so did ERLIN2 knockdown. More importantly, the impacts of SNHG17 down-regulation on the malignant behaviors of astrocytoma cells were counteracted by overexpressed ERLIN2 or inhibited miR-876-5p.

CONCLUSIONS

SNHG17 could induce the progression of astrocytoma by sponging miR-876-5p to elevate the expression of ERLIN2. This study indicated that SNHG17 has a high potential to be a therapeutic target for astrocytoma.

摘要

背景

星形细胞瘤是原发性中枢神经系统中常见的肿瘤类型,在全球范围内死亡率较高。越来越多的研究表明,长链非编码 RNA(lncRNA)的异常表达导致了多种癌症的发生。

方法

通过 RT-qPCR 检测 SNHG17、miR-876-5p 和 ERLIN2 的表达,通过 Western blot 检测 ERLIN2 蛋白水平。通过 RNA 下拉和荧光素酶报告基因实验说明了 SNHG17 与其下游分子之间的关系。

结果

SNHG17 在星形细胞瘤细胞中上调。此外,沉默 SNHG17 可以抑制星形细胞瘤细胞的增殖、迁移和侵袭。此外,miR-876-5p 被选为星形细胞瘤中 SNHG17 的下游分子。ERLIN2 被确定为 miR-876-5p 的靶基因。miR-876-5p 过表达和 SNHG17 沉默降低了 ERLIN2 的 mRNA 和蛋白水平。此外,miR-876-5p 过表达减缓了星形细胞瘤细胞的生物学过程,而 ERLIN2 敲低也是如此。更重要的是,过表达 ERLIN2 或抑制 miR-876-5p 可以逆转 SNHG17 下调对星形细胞瘤细胞恶性行为的影响。

结论

SNHG17 通过海绵吸附 miR-876-5p 升高 ERLIN2 的表达,从而诱导星形细胞瘤的进展。本研究表明,SNHG17 具有成为星形细胞瘤治疗靶点的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb7/7469335/89ff71e01bbe/12885_2020_7280_Fig1_HTML.jpg

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