<p>Suppression of miR-21-3p enhances TRAIL-mediated apoptosis in liver cancer stem cells by suppressing PI3K/Akt/Bad cascade via regulating PTEN</p>

Abstract

BackgroundTNF-related apoptosis-inducing ligand (TRAIL) functions as a selective apoptosis-inducing ligand in cancer cells with normal cells remaining unaffected; however, resistance limits its anticancer properties. Cancer stem cells (CSCs) are involved in the treatment of resistant cancer cases including liver cancer (LC). The aim of this study was to look into the approaches for increasing the sensitivity of liver cancer stem cells (LCSCs) toward TRAIL.MethodologyPLC, HepG2 and Huh7 LC cell lines were used in this study. Quantitative reverse transcription PCR (qRT-PCR) analysis was done for evaluating the expression of miR-21-3b. Fluorescent-activated cell-sorting equipment was used for separation and identification of LCSCs and non-LCSCs. The cells were transfected with RNA along with miR-21-3p mimics, anti- miR-21-3p, miR-NC and the phosphatase and tensin homologue (PTEN) siRNA. MTT assay for cell viability, Luciferase assay for luciferase activity, Western blots for the expression of proteins and flow cytometry for the measurement of ROS and apoptosis, respectively, were carried out. Tumor xenografts nude mice were used for tumor growth in vivo.ResultsWe found that miR-21-3p was overexpressed in LCSCs compared to non-LCSCs and that the suppression of miR-21-3p along with anti-miR-21-3p enhanced the sensitivity of LCSCs to TRAIL-mediated apoptosis. We further found that miR-21-3p regulated the expression of PTEN in Huh7-LCSCs directly and that the suppression of miR-21-3p enhanced the levels of PTEN. The study confirmed that inhibition of the PI3K/Akt/Bad signaling pathway was involved in enhancing TRAIL-mediated apoptosis of LC cells.ConclusionThe study suggested that overexpression of miR-21-3p suppresses the sensitivity to TRAIL in LCSCs. This study concludes that the suppression of miR-21-3p is a potential approach for enhancing the sensitivity of LC cells toward TRAIL by PI3K/Akt/Bad cascade via the miR-21-3p/PTEN axis.

Chemotherapeutic Stress Influences Epithelial–Mesenchymal Transition and Stemness in Cancer Stem Cells of Triple-Negative Breast Cancer

“…MiR-192-5p was significantly abolished in hepatocellular carcinomas expressing high levels of CSC markers, but enhanced doxorubicin sensitivity in breast cancer [51,52]. MiR-21-3p played an important role in mediating cisplatin resistance in ovarian cancer and reduced TRAIL-mediated apoptosis in liver cancer stem cell [34,35]. Mir-155-5p suppressed EMT in breast cancer but enhanced metastasis in oral squamous cell carcinoma [27,28].…”

Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

“…lncRNA GAS5 regulates the radiosensitivity of A549 cells through the miR-21/PTEN/Akt axis. PTEN is one of the most important target proteins of miR-21, and the miR-21/PTEN/Akt axis has been revealed to play a crucial role in various cellular activities (27)(28)(29)(30). In this experiment, the activation of the PTEN/Akt pathway was also assessed in our experimental model.…”

MiR-21-3p Promotes Hepatocellular Carcinoma Progression Through Regulating Smad7/Yap1

“…MiRNAs are considered to be biomarkers of diagnosis and prognosis since discovered (6). MiR-21-3p was demonstrated to inhibit cell apoptosis rate in liver cancer stem cells via directly regulating PTEN (7). Our miRNA microarray analysis results displayed that miR-21-3p is signi cantly upregulated in HCC.…”