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BBOX1-AS1 通过海绵吸附 hsa-miR-361-3p 并靶向 SH2B1 促进结直肠癌的进展。

BBOX1-AS1 contributes to colorectal cancer progression by sponging hsa-miR-361-3p and targeting SH2B1.

机构信息

Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, China.

Information Section, Armed Police Hubei Provincial Corps Hospital, Wuhan, China.

出版信息

FEBS Open Bio. 2022 May;12(5):983-992. doi: 10.1002/2211-5463.12802. Epub 2022 Mar 26.

Abstract

Colorectal cancer (CRC) is the third main cause of cancer-relevant deaths worldwide, and its incidence has increased in recent decades. Previous studies have indicated that certain long noncoding RNAs (lncRNAs) have regulatory roles in tumor occurrence and progression. Often, lncRNAs are competitive endogenous RNAs that sponge microRNAs to up-regulate mRNAs. Here, we examined the role of a novel lncRNA gamma-butyrobetaine hydroxylase 1 antisense RNA 1 (BBOX1-AS1) in CRC. We observed that BBOX1-AS1 is overexpressed in CRC cell lines, and BBOX1-AS1 knockdown enhances cell proliferation, migration and invasion while reducing cell apoptosis. miR-361-3p is present at a low level in CRC and is negatively modified by BBOX1-AS1. Moreover, miR-361-3p was validated to be targeted by BBOX1-AS1. Src homology 2 B adaptor protein 1 (SH2B1) was notably upregulated in CRC cell lines and was identified as a downstream gene of miR-361-3p. In addition, we found that miR-361-3p amplification can suppress the expression of SH2B1. Finally, data from rescue assays suggested that overexpression of SH2B1 counteracted BBOX1-AS1 silencing-mediated inhibition of CRC progression. In conclusion, BBOX1-AS1 promotes CRC progression by sponging hsa-miR-361-3p and up-regulating SH2B1.

摘要

结直肠癌(CRC)是全球癌症相关死亡的第三大主要原因,其发病率在近几十年来有所增加。先前的研究表明,某些长非编码 RNA(lncRNA)在肿瘤发生和进展中具有调节作用。通常,lncRNA 是竞争性内源性 RNA,可通过海绵吸附 microRNA 来上调 mRNAs。在这里,我们研究了新型 lncRNA γ-丁酰甜菜碱羟化酶 1 反义 RNA 1(BBOX1-AS1)在 CRC 中的作用。我们观察到 BBOX1-AS1 在 CRC 细胞系中过度表达,BBOX1-AS1 敲低可增强细胞增殖、迁移和侵袭,同时减少细胞凋亡。miR-361-3p 在 CRC 中表达水平较低,受 BBOX1-AS1 的负调控。此外,miR-361-3p 被验证为 BBOX1-AS1 的靶标。Src 同源 2B 衔接蛋白 1(SH2B1)在 CRC 细胞系中显著上调,并被鉴定为 miR-361-3p 的下游基因。此外,我们发现 miR-361-3p 扩增可抑制 SH2B1 的表达。最后,挽救实验的数据表明,SH2B1 的过表达可抵消 BBOX1-AS1 沉默介导的对 CRC 进展的抑制作用。总之,BBOX1-AS1 通过海绵吸附 hsa-miR-361-3p 并上调 SH2B1 促进 CRC 进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb6/9063435/458243e7dbab/FEB4-12-983-g002.jpg

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