title: Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets‑1 network in triple-negative breast cancer.
abstract: 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 β3 integrin-mediated cell- extracellular matrix interactions restrained triple-negative breast cancer (TNBC) growth, and elevated β3 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 β3 integrin in TNBC samples. Furthermore, bioinformatics analysis revealed the putative miR-30 binding sites in the 3'-UTR of β3 integrin. Results of luciferase assay revealed a strong repression of luciferase activity after transfection with miR‑30a-5p and wild-type 3'-UTR of β3 integrin. In TNBC cells, miR-30a-5p promoted an epithelial phenotype and suppressed invasion by specifically targeting β3 integrin subunit to subsequently interdict the β3 integrin/Erk/Ets-1 network.
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Wentong
authors.initials: W
authors.lastname: Li
authors.affiliation: The Third Department of Health Care, Weifang People's Hospital, Weifang, Shandong 261053, P.R. China.
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Medical Biology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhai
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Lv
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000378:metabolism*; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010957:Plasmids / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C494041:ETS1 protein, human; C061248:ITGB3 protein, human; D039661:Integrin beta3; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1; D048049:Extracellular Signal-Regulated MAP Kinases