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长链非编码 RNA ABHD11-AS1 通过调节 miR-133a/SOX4 轴促进结直肠癌的发展。

Long non-coding RNA ABHD11-AS1 promotes colorectal cancer development through regulation of miR-133a/SOX4 axis.

机构信息

Radiology Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an city, Shaanxi Province, P.R. China.

Department of MRI, Shaanxi Provincial People's Hospital, Xi'an city, Shaanxi Province, P.R. China.

出版信息

Biosci Rep. 2018 Dec 14;38(6). doi: 10.1042/BSR20181386. Print 2018 Dec 21.

Abstract

Recently, lncRNA has been verified to regulate the development and progression of tumor. LncRNA ABHD11-AS1 has been proven to serve as an oncogene in several cancers. However, the role of ABHD11-AS1 in colorectal cancer remains totally unknown. In the present study, qRT-PCR assay revealed that ABHD11-AS1 expression was markedly higher in colorectal cancer tissues and cell lines. In addition, patients who displayed overexpression of ABHD11-AS1 showed a significantly poorer progression free survival (PFS) and overall survival (OS) by Kaplan-Meier analysis. Loss-of-function experiments suggested that silencing of ABHD11-AS1 expression could significantly reduce the proliferation, colony formation, migration and invasion of colorectal cancer cells, and increase cell apoptosis. Moreover, bioinformatics analysis, biotin pull-down assay, luciferase reporter assay, and RIP assay disclosed that ABHD11-AS1 straightly interacted with miR-133a. We also found that SOX4 was a downstream target of miR-133a and ABHD11-AS1 subsequently exerted its biological effects via modulating the expression of SOX4 in colorectal cancer cells. Collectively, these findings manifested that the ABHD11-AS1/miR-133a/SOX4 axis may be a cogitable and promising therapeutic target for colorectal cancer.

摘要

最近,lncRNA 已被证实可调节肿瘤的发生和发展。lncRNA ABHD11-AS1 已被证明在几种癌症中作为癌基因发挥作用。然而,ABHD11-AS1 在结直肠癌中的作用仍完全未知。在本研究中,qRT-PCR 检测显示 ABHD11-AS1 在结直肠癌组织和细胞系中表达明显升高。此外,通过 Kaplan-Meier 分析,ABHD11-AS1 表达过度的患者无进展生存期(PFS)和总生存期(OS)明显较差。功能丧失实验表明,沉默 ABHD11-AS1 的表达可显著降低结直肠癌细胞的增殖、集落形成、迁移和侵袭能力,并增加细胞凋亡。此外,生物信息学分析、生物素下拉实验、荧光素酶报告实验和 RIP 实验表明 ABHD11-AS1 可与 miR-133a 直接相互作用。我们还发现 SOX4 是 miR-133a 的下游靶基因,ABHD11-AS1 随后通过调节结直肠癌细胞中 SOX4 的表达发挥其生物学作用。总之,这些发现表明 ABHD11-AS1/miR-133a/SOX4 轴可能是结直肠癌一个有价值的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49e0/6294614/dc324fd094e6/bsr-38-bsr20181386-g1.jpg

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