MicroRNA‑125a‑5p controls the proliferation, apoptosis, migration and PTEN/MEK1/2/ERK1/2 signaling pathway in MCF‑7 breast cancer cells

Abstract

MicroRNA (miR)-125a-5p has shown the potential for suppressing tumorigenesis and development; however, the effects of miR-125a-5p on breast cancer cells remains unknown. The aim of this study was to evaluate the effects and underlying mechanisms of miR-125a-5p in MCF-7 breast cancer cells. MCF-7 cells were transfected with miR-125a-5p mimic or miR-125a-5p small interfering RNA to produce miR-125a-5p overexpressing/knockdown cells. Cell proliferation was assessed by an MTT assay, and cell migration ability was determined by an in vitro scratch assay. Hoechst 33258 staining and flow cytometry were performed to assess the effects of miR-125a-5p on MCF-7 apoptosis. Western blotting and reverse transcription-quantitative polymerase chain reaction were used for measuring phosphatase and tensin homolog (PTEN), phosphorylated (p)-mitogen-activated protein kinase kinase (MEK1/2)/MEK1/2, p-ERK1/2/ERK1/2, B-cell lymphoma-2 (Bcl-2), cleaved caspase-3, and miR-125a-5p expression. miR-125a-5p overexpression inhibited the proliferation and migration, but promoted the apoptosis of MCF-7 cells. These effects were associated with increases in PTEN and cleaved caspase-3 expression, and decreases in p-MEK1/2/MEK1/2, p-ERK1/2/ERK1/2, and Bcl-2. Silencing of miR-125a-5p exhibited opposing effects on MCF-7 cells. These observations suggested that miR-125a-5p participates in the regulation of multiple functions of MCF-7 cells by promoting the expression of PTEN tumor suppressor genes, activating MEK1/2/ERK1/2 signaling, and regulating caspase-3/Bcl-2 signaling. Thus, it may be a suitable target for breast cancer gene therapy.

RETRACTED:CircFBXW7alleviates glioma progression through regulatingmiR‐23a‐3p/PTENaxis

“…Similarly, our studies revealed that miR‐23a‐3p suppresses U251 cell growth and metastasis by targeting PTEN. In addition, several studies have shown that PTEN is negatively correlated with the high invasiveness of cancer cells (Salvatore et al, 2019), for example, upregulation of PTEN was found to suppress cell migration and invasion by blocking the PI3K/Akt pathway in non‐small cell lung cancer (Liao et al, 2019) and hepatocellular carcinoma (Kannan et al, 2019), and inactivation of MEK1/ERK1 in breast cancer (Liang et al, 2019). The above results suggest that the overexpression of PTEN may be an excellent clinical treatment method for glioma.…”

Targeting CD82/KAI1 for Precision Therapeutics in Surmounting Metastatic Potential in Breast Cancer

“…Further studies have revealed that miR-124 could inhibit breast cancer invasion, and metastasis [111,112]. miR-125a-5p was significantly downregulated in breast cancer, concomitant with a lower overall free survival and progression-free survival [113], and observed to suppress breast cancer cell proliferation and migration [114]. Interestingly, miR-125a-5p was able to overcome chemoresistance when paired with chemotherapeutic drugs [115].…”

Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer

“…The overexpression of miR-125a-5p increases PTEN expression and significantly reduces phosphorylated MEK and ERK expressions and suppression in cell proliferation and migration in MCF-7. Using Hoechst staining, flow cytometry and Western blot, miR-125a-induced apoptosis was shown to be mediated by caspase-3 cleavage and decreased in the Bcl-2 level [104]. Two recent papers also demonstrated the role of miR-125 as a drug-resistant sensitizer.…”