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长链非编码RNA DANCR- miR-758-3p-PAX6分子网络调控乳腺癌细胞的凋亡和自噬

LncRNA DANCR-miR-758-3p-PAX6 Molecular Network Regulates Apoptosis and Autophagy of Breast Cancer Cells.

作者信息

Zhang Xian Hu, Li Bing Feng, Ding Jie, Shi Lei, Ren Huo Ming, Liu Kui, Huang Chuan Cai, Ma Fu Xiao, Wu Xin Yao

机构信息

Department of General Surgery, Suzhou First People's Hospital, Suzhou, Anhui 234000, People's Republic of China.

Physical Examination Department, Suzhou Central Blood Station, Suzhou, Anhui 234000, People's Republic of China.

出版信息

Cancer Manag Res. 2020 May 29;12:4073-4084. doi: 10.2147/CMAR.S254069. eCollection 2020.

Abstract

OBJECTIVE

This study set out to probe into the effects of long non-coding RNA (LncRNA) differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis and autophagy of breast cancer (BC) cells.

METHODS

The expression levels of DANCR, miR-758-3p and paired box 6 (PAX6) in BC tissues and cell lines were detected. The transcription and protein levels of PAX6, apoptosis-related factors (caspase-3, caspase-9, Bax/Bcl-2), and autophagy-related factors (LC3B, Atg5, Beclin-1) in BC cells were detected. The cell proliferation, apoptosis, autophagy and the regulatory relationship between genes and target genes were analyzed.

RESULTS

DANCR and PAX6 were up-regulated in BC tissues and cell lines, while miR-758-3p was opposite. Down-regulating DANCR inhibited the malignant proliferation of BC cells and also promoted apoptosis and autophagy, which showed that caspase-3, caspase-9, Bax/Bcl-2, LC3B, Atg5 transcription and protein levels increased, while Beclin-1 transcription and protein levels decreased. DANCR regulated miR-758-3p in a targeted manner, and its over-expression could weaken the anti-cancer effect of miR-758-3p on BC cells. In addition, miR-758-3p also directly targeted PAX6, and knocking down its expression could weaken the inhibitory effect of down-regulating PAK6 on BC cell apoptosis and autophagy. We also found that DANCR acted as a competitive endogenous RNA sponge miR-758-3p, thus regulating the PAX6 expression.

CONCLUSION

DANCR-miR-758-3p-PAX6 molecular network plays a key regulatory role in BC cell apoptosis and autophagy, which may provide reference for treating patients.

摘要

目的

本研究旨在探讨长链非编码RNA(LncRNA)分化拮抗非蛋白质编码RNA(DANCR)对乳腺癌(BC)细胞凋亡和自噬的影响。

方法

检测BC组织和细胞系中DANCR、miR-758-3p和配对盒6(PAX6)的表达水平。检测BC细胞中PAX6、凋亡相关因子(caspase-3、caspase-9、Bax/Bcl-2)和自噬相关因子(LC3B、Atg5、Beclin-1)的转录和蛋白水平。分析细胞增殖、凋亡、自噬以及基因与靶基因之间的调控关系。

结果

DANCR和PAX6在BC组织和细胞系中上调,而miR-758-3p则相反。下调DANCR可抑制BC细胞的恶性增殖,还可促进凋亡和自噬,表现为caspase-3、caspase-9、Bax/Bcl-2、LC3B、Atg5转录和蛋白水平升高,而Beclin-1转录和蛋白水平降低。DANCR以靶向方式调控miR-758-3p,其过表达可削弱miR-758-3p对BC细胞的抗癌作用。此外,miR-758-3p也直接靶向PAX6,敲低其表达可削弱下调PAK6对BC细胞凋亡和自噬的抑制作用。我们还发现DANCR作为竞争性内源性RNA海绵吸附miR-758-3p,从而调控PAX6表达。

结论

DANCR-miR-758-3p-PAX6分子网络在BC细胞凋亡和自噬中起关键调控作用,可为治疗患者提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c76c/7269637/33fdfdfbab8d/CMAR-12-4073-g0003.jpg

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