lncRNA-miRNA/RBP-mRNA Network Involved in Human Triple-Negative Breast Cancer: An Integrated Approach

Noncoding RNA regulatory networks play crucial roles in human breast cancer. The aim of this study was to establish a network containing multi-type RNAs and RBPs in triple-negative breast cancer (TNBC). Differential expression analyses of lncRNAs, miRNAs, and genes were performed using the GEO2R tool. Downstream RBPs and miRNAs were identified using respective databases. GO, KEGG, and protein-protein interaction were predicted. Expression of mRNAs, lncRNAs, and miRNAs were examined using TCGA and ENCORI. TMEM161B-AS1-miR-3646-SERPINB5 axis was validated with the expression level and cell function. TMEM161B-AS1-RBFOX1-SER-PINB5 axis was validated using RIP assays. A lncRNA-miRNA-mRNA network, a lncRNA-RBP-mRNA network, and a lncRNA-miRNA/RBP-mRNA network were constructed. Alterations in the expression levels of TMEM161B-AS1, miR-3646, and SERPINB5 were confirmed by real-time polymerase chain reaction as downregulation, upregulation, and downregulation, respectively. TMEM161B-AS1 inhibited TNBC cell proliferation, migration, and invasion. miR-3646 reversed the inhibitory effect of TMEM161B-AS1 on cell function, while SERPINB5 offset the miR-3646 effect. RB-FOX1 bound to SERPINB5 mRNAs, and TMEM161B-AS1 was involved in their interaction. This study revealed the ln-cRNA-miRNA/RBP-mRNA network in TNBC, providing more directions to study the molecular mechanism of TNBC.