LncRNA MIR4435-2HG promotes proliferation, migration, invasion and epithelial mesenchymal transition via targeting miR-22-3p/TMEM9B in breast cancer.

Objective: Breast cancer, as a malignancy with the highest incidence and mortality in women, seriously threatens women's life and health. Pieces of evidence have suggested that long non-coding RNAs (lncRNAs) possess important roles in regulating the occurrence and development of breast cancer.

Methods: RT-qPCR was used to explore the expression levels of MIR4435-2HG, miR-22-3p and TMEM9B in breast cancer tissues and cell lines. Cell viability, proliferation, migration and invasion were assessed by CCK-8 assay, Colony formation assay, Wound healing assay and Transwell assay, respectively. The effect of MIR4435-2HG on EMT progress was explored by Immunofluorescence assay and Western blot. RNA pull-down analysis and Dual-luciferase reporter assay were performed to validate the interaction between MIR4435-2HG and miR-22-3p, as well as miR-22-3p and TMEM9B.

Results: MIR4435-2HG was notably up-regulated in breast cancer tissues and cell lines. Additionally, down-regulation of MIR4435-2HG restrained the viability, proliferation, migration, invasion and EMT of breast cancer cells. MiR-22-3p expression was down-regulated in breast cancer tissues and cell lines, and negatively associated with MIR4435-2HG expression. Over-expression of miR-22-3p obviously inhibited the viability, proliferation, migration, invasion and EMT of breast cancer cell lines. Furthermore, TMEM9B was up-regulated in breast cancer tissues and cell lines and negatively associated with miR-22-3p expression. 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.

Conclusion: MIR4435-2HG plays a potential tumor-promoting role in the occurrence and development of breast cancer, possibly by regulating the miR-22-3p/TMEM9B axis.