LncRNA MIR4435-2HG Promotes Proliferation, Migration, Invasion and EMT Via Targeting miR-22- 3p/TMEM9B in Breast Cancer

Background: Breast cancer, as the malignancy with the highest incidence rate and mortality rate in women, seriously threatens human life and health. Pieces of evidence have suggested that long non-coding RNAs (lncRNAs) possess important effects on regulating the occurrence and development of breast cancer. Results: : In the present study, MIR4435-2HG was highly expressed in breast cancer tissues and cells. Down-regulation of MIR4435-2HG inhibited the viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of breast cancer cell lines by Cell Counting Kit-8 (CCK-8), colony formation, transwell migration and invasion, immunofluorescence and western blot assays. Dual-luciferase reporter assay and RNA pull-down analysis confirmed that miR-22-3p was a target of MIR4435-2HG. Over-expression of MicroRNA-22-3p (miR-22-3p) obviously inhibited the viability, proliferation, migration, invasion and EMT of breast cancer cell lines. Transmembrane protein 9 domain family member B (TMEM9B) was up-regulated in breast cancer tissues and cell lines. Dual-luciferase reporter assay confirmed that TMEM9B was a target of miR-22-3p. TMEM9B inhibition partially restored the effects of MIR4435-2HG/miR-22-3p on the viability, proliferation, migration, invasion and EMT of breast cancer cell lines. Conclusions: : MIR4435-2HG potentially played a tumor-promoting role in the occurrence and development of breast cancer, which might be achieved by regulating the miR-22-3p/TMEM9B axis.