Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets‑1 network in triple-negative breast cancer
Authors: Wentong Li
Chuanliang Liu
Chunling Zhao
Limin Zhai
Shijun Lv
Journal: International Journal of Oncology (2016)
Discipline: CLINICAL MEDICINE
Keywords: Integrins; β3 integrin; triple-negative breast cancer (TNBC); miR-30a-5p; Erk/Ets-1 signaling pathways
Affiliations: Department of Pathology, Weifang Medical University, Weifang, Shandong 261053, P.R. China., The Third Department of Health Care, Weifang People's Hospital, Weifang, Shandong 261053, P.R. China., Department of Medical Biology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.

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. 

Retracted: No

PubPeer comments:
 In Stevenson et al 2021 u201cThe impact of contraceptive access on high school graduationu201d in Science Advances, some numbers do not add up. In the Supplementary Material, Table S1 lists the pre-intervention Other, non-Hispanic cohort size in the 2010 US Census and 2009 through 2017 1-year American Community Survey data as 300, but Table S2 as 290 = 100+70+30+90 (Black + Asian + American Indian + Other Multiple Races). The post-intervention cohort size is 200 in Table S1, but 230 in Table S2, so the difference is in the other direction (S2 larger) and cannot be due to the same adjustment of one Table for both cohorts, e.g. omitting some racial group or double-counting multiracial people. It is interesting that the graduation rate for the Other race group is omitted from the main paper and the Supplementary Material Table S3, because by my calculations , in Colorado, the Other graduation rate decreased after the CFPI contraception access expansion, but in the Parallel Trends states (the main comparison group of US states that the authors use), the Other graduation rate increased significantly. The one missing row in the Table is exactly the one in which the results are the opposite to the rest of the paper and the conclusions of the authors. ,