Breast cancer is the most aggressive and fatal form of cancer among women globally. Although the role of some miRNAs that are often dysregulated in breast cancer has been deciphered, the regulatory function of others still remains unknown. The current study was aimed at determining the biological role and underlying mechanism of miR-548k in breast cancer. In this study, the significant overexpression of miR-548k in breast cancer tissues compared to adjacent normal tissues was confirmed. Also, bioinformatics analysis indicated that PTEN, as a negative regulator of PI3K/AKT signaling pathway, was a potential target of miR-548k, and its expression was downregulated in breast cancer tissues rather than normal tissues. Furthermore, the ectopic increase of miR-548k decreased the expression of PTEN in breast cancer, suggesting that PTEN is one of the potential downstream targets of miR-548k. Besides, functional analysis was conducted to assess the capability of miR-548k to alter apoptosis along with the changed expression levels of miR-548k in breast cancer cells. Based on this investigation, forced increase of miR-548k disrupted programmed cell death in MCF-7 cells. Apart from this, in silico study of miR-548 family supported its association with the main components of PI3K/Akt signaling pathway, opening a prospective research area in cancer therapy. In brief, suppression of PTEN partly mediated by miR-548k diminished apoptosis and promoted cell proliferation through PI3K/Akt pathway in breast cancer, suggesting a novel therapeutic axis, miR-548k/PTEN/ PI3K/Akt, for treatment of breast cancer in the future.
Keywords: Apoptosis; Breast cancer; PI3K/Akt; PTEN; miR-548k.
© 2022 International Union of Biochemistry and Molecular Biology.