Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets-1network in triple-negative breast cancer

Integrins are adhesion receptors involved in bidirectional signaling and are crucial for various cellular responses during normal homeostasis and pathological conditions, such as cancer progression and metastasis. In the present study, we demonstrated that blockage of beta 3 integrin-mediated cell-extracellular matrix interactions restrained triple-negative breast cancer (TNBC) growth, and elevated beta 3 integrin can trigger the rewiring of Erk/Ets-1 signaling pathways, thereby enhancing cell growth and invasion. Ectopic expression of miRNA has been implicated in the deregulation of integrin expression and activity, blocking of cancer tumor development and progression, and acquisition of metastatic phenotype. miR-30a-5p expression has been implicated in the progression of breast cancer. Overexpression of miR-30a-5p suppressed the proliferation, migration and invasion of breast cancer cells. On the contrary, inhibition of miR-30a-5p promoted the proliferation, migration, and invasion of TNBC cells by suppressing the expression of ERK/Ets-1 signal. An inverse correlation was found between the mRNA expressions of miR-30a-5p and beta 3 integrin in TNBC samples. Furthermore, bioinformatics analysis revealed the putative miR-30 binding sites in the 3'-UTR of beta 3 integrin. Results of luciferase assay revealed a strong repression of luciferase activity after transfection with miR-30a-5p and wild-type 3'-UTR of beta 3 integrin. In TNBC cells, miR-30a-5p promoted an epithelial phenotype and suppressed invasion by specifically targeting beta 3 integrin subunit to subsequently interdict the beta 3 integrin/Erk/Ets-1 network.