ABSTRACT
Objective:To investigate the significance and regulatory mechanism of miR-142-3p and ER1 in serum and placenta of pregnant women with gestational diabetes mellitus (GDM) complicated with preeclampsia (PE) in the occurrence and development of disease.Methods:A total of 198 pregnant women admitted from Jun. 2019 to Jun. 2020 were selected as the study subjects, including 66 pregnant women with GDM (GDM group) , 60 pregnant women with GDM complicated with PE (GDM+PE group) and 72 normal pregnant women (control group) . Clinical indicators were detected and pregnancy outcome data were collected. The relative expression levels of miR-142 -3p and ER1 mRNA in serum and placental tissues of study subjects were determined by quantitative real-time polymerase link assay. The expression of ER1 protein in the placenta was detected by Western blot. Human choriotrophoblast cells HTR-8/SVneo were treated with miR-142-3p.Results:The expression levels of miR-142-3p in serum and placenta tissues in GDM+PE group were significantly lower than those in GDM+PE group and control group ( P<0.05) . The mRNA expression of ER1 in serum and placenta in GDM+PE group was significantly higher than that in GDM+PE group and control group ( P<0.05) . There was a significant negative correlation between the relative expression levels of miR-142-3p and ER1 mRNA in serum and placental tissues of pregnant women in the GDM+PE group ( r=-0.589 and -0.643, P=0.006 and < 0.001) .After transfection of HTR-8/SVneo cells with miR-142-3p, ER1 mRNA expression in the mimic group was 1.09±0.14,significantly lower than that of NC group (2.14±0.52) , inhibitor group (3.69±0.88) and inhibitor NC group (2.26±0.43) ( P<0.001) . The expression of DNMT1 in inhibitor group was significantly higher than that in the other three groups ( P<0.001) . Conclusion:In patients with GDM complicated with PE, miR-142-3p levels are reduced and ER1 levels are increased, which may be involved in the occurrence and progression of the disease.
ABSTRACT
MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.
ABSTRACT
Aim To explore the molecular mechanism of miR-142-3p involved in the regulation of chemosen-sitivity of breast cancer by targeting high-mobility group box 1 ( HMGB1 ). Methods Real-time quantitative PCR ( QPCR) was employed to detect the levels of miR-142-3p in human breast cancer MCF-7 cells and doxorubicin-resistant MCF-7/D0X cells. MIT was used to detect the proliferation of doxorubicin ( DOX)-treated groups. Flow cytometry was applied to detect the apoptotic rate of each group after transfection. Western blot was used to detect the expression of HMGB1 and autophagy-related proteins. Double Lucif-erase Report experiment was carried out to evaluate the targeting effect of miR-142-3p on HMGB1. Results The level of miR-142-3p in MCF-7/D0X cells was sig nificantly down-regulated. Overexpression of miR-142-3p enhanced the sensitivity of breast cancer cells to DOX and increased the apoptotic rate induced by DOX. HMGB1 was the direct functional target of miR-142-3p in breast cancer cells,and the overexpression of HMGB1 could significantly relieve the promotion of ap-optosis and inhibition of autophagy by miR-142-3p uP-regulation. Conclusions The overexpression of miR-142-3p may enhance the chemosensitivity of breast cancer cells to DOX by inhibiting autophagy and targeting HMGB1. miR-142-3p/HMGBl provides a new target for reversing the drug resistance of breast cancer.
ABSTRACT
microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 μg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.