Silencing DSCAM-AS1 suppresses the growth and invasion of ER-positive breast cancer cells by downregulating both DCTPP1 and QPRT

• Published in: Aging (Albany, NY.) Vol. 12; no. 14; pp. 14754 - 14774
• Main Authors: Yue, Zhang, Shusheng, Jia, Hongtao, Song, Shu, Zhao, Lan, Huang, Qingyuan, Zhang, Shaoqiang, Cheng, Yuanxi, Huang
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 27.07.2020
• Subjects: Adult; Aged; Apoptosis - genetics; Breast Neoplasms - genetics; Breast Neoplasms - therapy; Cell Line, Tumor; Disease Progression; Down Syndrome - genetics; Down-Regulation; Female; Gene Silencing; Histones - metabolism; Humans; MicroRNAs - genetics; Middle Aged; Pentosyltransferases - genetics; Pyrophosphatases - genetics; Receptors, Estrogen - metabolism; Research Paper; RNA, Long Noncoding - genetics; RNA, Long Noncoding - therapeutic use; miRNA; DSCAM-AS1; DCTPP1; H3K27 acetylation; QPRT
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.103538

Breast cancer (BC) remains a significant threat to the health of women; however, the mechanism underlying the initiation and progression of BC is poorly understood. We analyzed data from the Gene Expression Omnibus database and The Cancer Genome Atlas datasets to identify differentially expressed genes between BC and normal tissues. The roles of dCTP pyrophosphatase 1 (DCTPP1) and quinolinate phosphoribosyltransferase (QPRT) in BC cells were investigated after knocking down or overexpressing the genes. The regulatory effects of Down syndrome cell adhesion molecule antisense RNA 1 (DSCAM-AS1) on DCTPP1 and QPRT expression were determined using luciferase reporter, RNA immunoprecipitation, RNA pull-down, chromatin immunoprecipitation, and fluorescence hybridization assays. DCTPP1 and QPRT were overexpressed in BC compared to normal tissues. Overexpression of DCTPP1 and QPRT was associated with poor BC progression and promoted growth, migration, and invasion of MCF7 and T47D cells but inhibited apoptosis. DSCAM-AS1 increased QPRT expression via competitively binding miRNA-150-5p and miRNA-2467-3p. DSCAM-AS1 promoted gene transcription by affecting H3K27 acetylation and enhanced mRNA stability by binding to the 3' untranslated region, which collectively resulted in DCTPP1 overexpression. Overall, DSCAM-AS1 knockdown decreased both DCTPP1 and QPRT expression, inhibiting the growth, migration, and invasion of estrogen receptor-positive BC.