MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2
MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2
Blog Article
Background/Aims: Accumulating evidence revealed that microRNAs (miRNAs) have been demonstrated as critical molecules in tumor development and progression.MiR-26a, located in a fragile chromosomal region associated with various human cancer, has been reported to be involved in regulating various cellular process, such as proliferation, apoptosis and invasion through targeting multiple oncogene.Docetaxel-mediated chemotherapy has been applied in improving the survival and prognosis of patients with advanced lung adenocarcinoma (LAD).
However, chemoresistance remains a major impediment to clinical application of this agent.It has been presented that decreased miR-26a expression lead to cisplatin resistance and promoted growth and migration in human lung cancer.Enhancer of zeste homolog 2 (EZH2) is the target of miR-26a.
The present moen rothbury faucet study aimed to investigate the function of miR-26a/EZH2 in the acquisition of malignant behaviors of LAD.Methods: MiR-26a and EZH2 expression levels in the dcetaxel-insensitive groups (n = 19) and the docetaxel-sensitive groups (n = 18) were assessed by qRT-PCR.Colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays and western blotting were performed to assess the effects of miR-26a on proliferation, apoptosis and epithelial-to-mesenchymal (EMT) phenotypes in docetaxel resistant LAD cells in vitro.
Xenograft transplantation, immunohistochemistry, tunel assays and western blotting assays were employed to demonstrate the role of miR-26a in docetaxel resistant LAD cells in vivo.The expression level of EZH2 in docetaxel-resistant LAD cells and corresponding click here parental cells was detected by qRT-PCR and western blotting.The relationship between miR-26a and EZH2 was confirmed by luciferase reporter assay.
And rescue assays were performed to further confirm that miRNA-26a contributes to the acquisition of malignant behaviors of docetaxel-resistant LAD cells through targeting EZH2.Results: MiR-26a was significantly down-regulated in the dcetaxel-insensitive groups (n = 19) compared with the docetaxel-sensitive groups (n = 18) assessed by qRT-PCR.MiR-26a decreased the proliferation, increased the apoptosis rate and reversed EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro.
EZH2 was confirmed as target of miR-26a.Rescue assays further verified that the function of miR-26a exerts in docetaxel-resistant LAD cells is through targeting EZH2.Conclusions: Our data revealed that overexpression of miR-26a in docetaxel-resistant LAD cells could decrease the proliferation, increase the apoptosis rate and reverse EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro and such function is partially exerted via downregulating EZH2.
MiR-26a/EZH2 signal pathway makes contribute to the malignant phenotype of docetaxel-resistant of LAD cells which indicated that miR-26a exerts pivotal functions in the molecular etiology of chemoresistant lung adenocarcinoma.