Two lncRNAs, MACC1-AS1 and UCA1, co-mediate the expression of multiple mRNAs through interaction with individual miRNAs in breast cancer cells

Abstract

Background: Increasing studies have shown that lncRNAs often play roles through interaction with miRNAs to control gene expression by inhibiting translation or facilitating degradation of target mRNAs. Here, we report that two lncRNAs, MACC1-AS1 and UCA1 are coordinately expressed in breast cancer cells and share the ability to interact with multiple miRNAs to mediate the expression of different genes. Methods: Targetscan, starBase and miRDB databases were used to predict the relationships of MACC1-AS1/UCA1-miRNA-mRNA network. qRT-PCR, and RNA sequencing were used to study the differential expression of lncRNAs and miRNA-targeted genes in breast cancer cells. RIP, RNA pull-down and luciferase assays were performed to confirm the molecular interactions of MACC1-AS1 or UCA1 with predicted miRNAs. The role of lncRNA-mediated miRNA-mRNA interactions in cell proliferation was examined by MTT assays following loss-of-function and gain-of-function effects. Results: We identified a lncRNA-miRNA-mRNA regulatory network in breast cancer cells, in which a number of mRNAs can be co-regulated by MACC1-AS1 and UCA1 lncRNAs. Each lncRNA possesses the capacity as a ceRNA to compete with various mRNA-targeting miRNAs. Interaction of MACC1-AS1 or UCA1 with individual miRNAs is able to increase the expression of the same target mRNAs, such as TBL1X and MEF2D, thus affecting cancer-cell growth phenotype. Conclusions: Our study suggests that in each cell type, there is a balance of interactions between certain lncRNAs and miRNAs. Disrupting the balance would eventually affect the expression of miRNA-targeted genes and cell proliferation.

Keywords

• lncRNA-miRNA-mRNA regulatory network
• UCA1
• MACC1-AS1