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STAT5A 诱导 LINC01198 通过稳定 DGCR8 促进神经胶质瘤细胞的增殖。

STAT5A induced LINC01198 promotes proliferation of glioma cells through stabilizing DGCR8.

机构信息

Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, P.R. China.

Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, P.R. China.

出版信息

Aging (Albany NY). 2020 Apr 4;12(7):5675-5692. doi: 10.18632/aging.102938.

Abstract

BACKGROUND

LINC01198 has been suggested to be able to predict overall prognosis for glioma; however, it has been little described in glioma.

RESULTS

It was shown that LINC01198 was markedly enriched in neoplasmic tissues relative to normal controls; and that elevated LINC01198 significantly correlated with unfavorable overall prognosis. Moreover, activation of STAT5A, identified as transcription factor (TF), can induce the expression of LINC01198. DGCR8, a kind of RNA-binding proteins (RBPs), was identified to be able to bind with LINC01198 that can stabilize the DGCR8. Five differential miRNAs with most significant difference, including miR-21-5p, miR-34-5p, miR-1246, miR-4488 and miR-494, were obtainable after silencing of DGCR8.

CONCLUSIONS

Together, the data we presented here suggested that STAT5 induced LINC01198 promotes proliferation and motility of glioma cells through stabilizing DGCR8 in glioma cells.

METHODS

Expression of LINC01198 was appraised by quantitative PCR (qPCR) and in situ hybridization (ISH) in glioma clinical specimens, totaling 100 cases. Post hoc statistical analysis was conducted. , LINC01198 was stably silenced or re-expressed by transfection with lentiviral-based vectors. Chromatin-immunoprecipitation (CHIP) was applied to identify the relevant TFs that can bind with LINC01198, which was corroborated with electrophoretic mobility shift (EMSA) assay. RNA-immunoprecipitation (RIP) was used to identify the RNA-binding protein that can bind with LINC01198. Moreover, miRNA microarray was used to screen out differential miRNAs after silencing of DGCR8.

摘要

背景

已有研究表明 LINC01198 能够预测胶质瘤的总体预后,但在胶质瘤中描述较少。

结果

结果表明,LINC01198 在肿瘤组织中明显富集,而在正常对照组织中则较低;并且升高的 LINC01198 与不利的总体预后显著相关。此外,鉴定出的转录因子(TF)STAT5A 可激活 LINC01198 的表达。DGCR8 是一种 RNA 结合蛋白(RBP),可与 LINC01198 结合,从而稳定 DGCR8。沉默 DGCR8 后,可获得 5 个差异最显著的差异 miRNA,包括 miR-21-5p、miR-34-5p、miR-1246、miR-4488 和 miR-494。

结论

综上所述,我们这里提供的数据表明,STAT5 诱导 LINC01198 通过稳定 DGCR8 促进胶质瘤细胞的增殖和迁移。

方法

通过定量 PCR(qPCR)和原位杂交(ISH)评估 100 例胶质瘤临床标本中的 LINC01198 表达情况,进行事后统计分析。通过慢病毒载体转染稳定沉默或重新表达 LINC01198。应用染色质免疫沉淀(CHIP)鉴定可与 LINC01198 结合的相关 TF,并用电泳迁移率变动(EMSA)测定验证。应用 RNA 免疫沉淀(RIP)鉴定可与 LINC01198 结合的 RNA 结合蛋白。此外,通过沉默 DGCR8 筛选出差异 miRNA 的 microarray。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eff7/7185146/cf4d277d9489/aging-12-102938-g001.jpg

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