The regulatory effect of 6-TG on lncRNA-miRNA-mRNA ceRNA network in triple-negative breast cancer cell line.

Published on Feb 26, 2021in Bioscience Reports2.942
· DOI :10.1042/BSR20203890
Daoyu Zhang1
Estimated H-index: 1
(JLU: Jilin University),
Xinglan An10
Estimated H-index: 10
(JLU: Jilin University)
+ 1 AuthorsZiyi Li14
Estimated H-index: 14
(JLU: Jilin University)
Sources
Abstract
Breast cancer is one of the most prevalent and reoccurring cancer types that leads to death in women. Triple-negative breast cancer (TNBC) is difficult to treat due to the lack of therapeutic targets. Many studies have focused on identifying drugs for use as alternative treatments for breast cancer. Thioguanine (6-TG) exerts antitumor effects in cancer. Increasing evidence has demonstrated that ceRNAs are involved in cancer processes. However, the mechanism by which 6-TG regulates lncRNA-miRNA-mRNAs has not been elucidated. We evaluated the antitumor effect of 6-TG in MDA-MB-231 cells and comprehensively analyzed the RNA-Seq data of MDA-MB-231 cells treated with 6-TG. Our results showed that most tumor pathways were blocked by 6-TG. The hub genes were FN1, FLNA, FLNB, VCL, GSN, MYH10, ACTN4, KDR and EREG, and they were all downregulated after 6-TG treatment. The coexpression network consisted of 18 miRNAs, 9 lncRNAs and 20 mRNAs. Hsa-mir-16-5p and Hsa-mir-335-5p targeted the greatest number of mRNAs in the network. These molecules could bind to PAX8-AS1 and eliminate the inhibition of target mRNA expression. We showed that PAX8-AS1 is the main lncRNA affected by 6-TG and that PAX8-AS1 regulates the hub genes in tumor pathways by competitively binding with miR-16-5p and miR-335-5p.
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