MicroRNA-1179 regulates proliferation and chemosensitivity of human ovarian cancer cells by targeting the PTEN-mediated PI3K/AKT signaling pathway

Abstract

Introduction: Owing to widespread roles of miRs, the dysregulation of their expression in human tissues has been linked with the development of several diseases such as cancer. The study was designed to investigate the role and therapeutic potential of miR-1179 in ovarian cancer. Material and methods: Proliferation rate was monitored by MTT assay. Transfections were performed using Lipofectamine 2000 reagent. Cell cycle apoptosis was detected by AO/EB and annexin V/PI staining. Expressions analysis was carried out by qRT-PCR and western blotting. In vivo evaluation was carried out in xenografted mouse models. Results: The results revealed that miR-1179 is considerably upregulated in ovarian cancer cell lines. Inhibition of miR-1179 triggers decrease in the viability via initiation of apoptotic cell death of ovarian PA-1 cancer cells. Tar-getScan analysis showed PTEN to be the main target of miR-1179 in PA-1 cells. Exploration of PTEN expression in ovarian cancer cell lines revealed up to 9-fold downregulation of PTEN. However, inhibition of miR-1179 in PA-1 cells resulted in upregulation of PTEN expression. In addition, overexpression of PTEN caused a reduction of PA-1 cell viability via induction of apoptotic cell death. However, silencing of miR-1179 could rescue the effects of miR-1179 inhibition on the proliferation of miR-1179. The miR-1179 suppression was accompanied by a significant decline in phosphorylation of PI3K and AKT expression in the PA-1 cells. The in vivo study showed that miR-1179 suppression inhibits the xenografted tumor growth. Conclusions: The results of this study indicate that miR-1179 may prove to be an important therapeutic target for ovarian cancer.

MicroRNA-1179 suppresses the proliferation and enhances vincristine sensitivity of oral cancer cells via induction of apoptosis and modulation of MEK/ERK and PI3K/AKT signalling pathways

“…The miR-1179 repression was found to inhibit proliferation and enhance the drug sensitivity of oral cancer cells to vincristine. Such implications have been drawn also previously (Zhihong et al 2019). The characterization of miR-1179 in oral cancer in this study revealed that autophagy is induced in oral cancer cells when miR-1179 transcript levels are repressed.…”

“…In the present study, miR-1179 was found to be upregulated in oral cancer cells which is in accordance with several previous studies (Peng et al 2011 , Krutovskikh et al 2010 ). Further, miR-1179 downregulation was previously been shown to decline the viability of ovarian cancer cells (Zhihong et al 2019 ). Similar, observations were made from the results of the current study.…”

“…Similarly, MEK/ERK pathway has shown to be activated in ovarian cancer (Zhang et al 2019 ). As such, the blockage of these signalling pathways is a vital asset to keep the cancer progression at check (Zhihong et al 2019 ). The miR-1179 suppression renders the MEK/ERK and PI3K/Akt pathways to proceed at fairly diminished rates by preventing the phosphorylation of crucial signalling components like MEK, ERK, PI3K and AKT.…”

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

“…Because prostate cancer chemotherapy is based primarily on the use of docetaxel, therapeutic increasing FAM46C expression can be combined with existing therapies to improve therapeutic efficacy. Increasing evidences have been shown that targeting PTEN and PI3K/AKT signaling pathway can inhibit or enhance chemosensitivity of several cancer types, including prostate cancer [24,38,39]. Therefore, we suggest that FAM46C may increase the chemosensitivity of prostate cancer cells to docetaxel through the PTEN/AKT signaling pathway, even though their roles are required for further investigation.…”

“…The clinical study found that the expression of PTEN protein in prostate cancer tissues was significantly lower than that in benign prostatic hyperplasia and negatively correlated to clinical Gleason score, pathological grade, and stage of prostate cancer [19,20], suggesting that PTEN protein decreases with the increase of the malignancy of prostate cancer. PI3K/AKT signaling activation can inhibit chemosensitivity and cell apoptosis and accelerate cell cycle progression, angiogenesis and cell invasion, while excessive PTEN expression can inhibit the activation of PI3K/AKT that inhibits P27 and Caspase-9 expression and promotes the translation from G1 to S phase [21][22][23][24]. Prostate cancer LNCaP cells exhibited PTEN inactivation, leading to constitutive activation of the AKT pathway [25].…”