MiR‐548k suppresses apoptosis in breast cancer cells by affecting PTEN/PI3K/AKT signaling pathway

Abstract

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.

Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition

“…Notably, most of the active compounds were more sensitive to HCC827 cells. In addition to HCC827 cells, PI3K was also overexpressed in other tested cells [ 29 , 30 , 31 , 32 ]. As to the reasons for the different sensitivity of the compounds to these tested cells, we hypothesized it might be because the PI3K pathway is not as equally important in the survival and proliferation of these cells as it is in HCC827 cells.…”

Inhibitory role of bone marrow mesenchymal stem cells‐derived exosome in non‐small‐cell lung cancer: microRNA‐30b‐5p, EZH2 and PI3K/AKT pathway

“…16 As a phosphatase, the tumour suppressor protein PTEN can dephosphorylate Akt and reduce its activation, and can block all downstream signalling events regulated by Akt, and is a negative regulator of PI3K. 39,40 Another study has reported that EZH2 can upregulate PI3K/AKT signalling pathway to aggravate chronic lymphocytic leukaemia. 41 PI3K/AKT signalling pathway, as one of the most significant intracellular pathways, affects cell survival and growth.…”

“…A previous study has demonstrated that EZH2 can promote H3K27me3 modification of PTEN promoter region, which inhibits PTEN expression and activates PI3K/AKT pathway to promote the proliferation and metastasis of NSCLC cells 16 . As a phosphatase, the tumour suppressor protein PTEN can dephosphorylate Akt and reduce its activation, and can block all downstream signalling events regulated by Akt, and is a negative regulator of PI3K 39,40 . Another study has reported that EZH2 can upregulate PI3K/AKT signalling pathway to aggravate chronic lymphocytic leukaemia 41 .…”

Research Progress of Resveratrol in Oral Cancer

“…Adenylate-activated protein kinase (AMPK) plays a regulatory role in many physiological processes of the body, such as autophagy, cell proliferation and differentiation, and apoptosis [18], Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway plays an important role in the proliferation, invasion and migration of a variety of tumors [19]. Chang [14] for the first time to demonstrate a pro-autophagic and apoptotic effects of resveratrol in cisplatin-resistant human oral cancer CAR cells, after the CAR cells were treated with 25 μM, 50 μM and 100 μM of resveratrol for 48h, The treated CAR cells were separately stained with the lysosomal red fluorescent probes LysoTracker Red DND-99 and MDC, it was found that CAR cells formed large numbers of autophagic vacuoles and apoptotic bodies, protein immunoblotting results revealed a significant increase in the protein expression of AMPK, Atg 5, Atg 12, Beclin-1, PI3K III, and LC3-II, The Akt expression is decreased.…”