MiR-512-3p regulates malignant tumor behavior and multi-drug resistance in breast cancer cells via targeting Livin

Abstract

Breast cancer (BCa) is one of the most lethal malignancies of female reproductive organs. Increasing evidence has revealed that miRNAs participate in both tumorigenesis and multi-drug resistance. MiR-512-3p, a small non-coding RNA (miRNA), was previously found to be upregulated in breast cancer cells. In this study, we first verified that miR-512-3p expression forced a significant reorganization of the tumor architecture, affecting important cellular processes involved in cell-cell contact, cell adhesion and cell motility. Accordingly, induction of miR-512-3p expression significantly enhanced chemosensitivity and decreased metastatic potential in BCa cells. Our study demonstrated that miR-512-3p directly targets the 3'UTR of Livin, thereby decreasing its expression in MCF-7 cells. MiR-512-3p overexpression significantly inhibited breast cancer cell growth and metastasis. Both miR-512-3p overexpression and Livin knockdown significantly increased the chemosensitivity of cancer cells. Epirubicin (EPB), gemcitabine (GCB) and docetaxel (TXT) had antitumor effects in vitro against human breast cancer cell lines, and miR-512-3p overexpression increased tumor sensitivity to these drugs. In addition, miR-512-3p overexpression significantly inhibited tumor growth in vivo. Collectively, our data suggest that miR-512-3p is a significant regulator of tumorigenesis and drug resistance in breast cancer and provides evidence that miR-512-3p may represent a promising target for breast cancer therapy.

Identification of Spindle and Kinetochore-Associated Family Genes as Therapeutic Targets and Prognostic Biomarkers in Pancreas Ductal Adenocarcinoma Microenvironment

“…MicroRNA, an endogenous small RNA with a length of about 20-24 nucleotides, has been implicated in human carcinogenesis (93). The miRNAs identified in our study have been associated with deteriorated neoplastic malignant phenotype such as proliferation, cell cycle, invasion, drug resistance, and angiogenesis (94)(95)(96)(97)(98). In fact, miR-185, miR-96, miR-218, miR-137, and miR-338 have been proven to exhibit therapeutic and prognostic value in PDAC, indicating that the SKA gene may be one of the target genes for these miRNAs (99)(100)(101)(102)(103).…”

Long non-coding RNA LINC00997 silencing inhibits the progression and metastasis of colorectal cancer by sponging miR-512-3p

“…Study has proven that miR-512-3p overexpression promotes the inhibition of metastasis in non-small cell lung cancer [ 29 ]. MiR-512-3p was reported to inhibit breast cancer cell growth and metastasis [ 30 ]. Above-mentioned research prompted further investigation into the role of LINC00997 and miR-512-3p in the metastasis of CRC.…”

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study

“…This miRNA was not prognostic neither predictive in the IRE cohort. However, it demostrated tumor suppressive and chemotherapy sensitizing effects in previous studies of BC [ 31 ]. Overall, results from this subset of analysis show that differential miRNA expression in the IRE cohort is only partly determined by patients’ heterogeneity, while it is mostly a function of inter-tumor differences.…”