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MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2.
Cell Physiol Biochem. 2017; 41(2):583-597.CP

Abstract

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 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 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.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

28214878

Citation

Chen, Jing, et al. "MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells Through Targeting EZH2." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 41, no. 2, 2017, pp. 583-597.
Chen J, Xu Y, Tao L, et al. MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2. Cell Physiol Biochem. 2017;41(2):583-597.
Chen, J., Xu, Y., Tao, L., Pan, Y., Zhang, K., Wang, R., Chen, L. B., & Chu, X. (2017). MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 41(2), 583-597. https://doi.org/10.1159/000457879
Chen J, et al. MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells Through Targeting EZH2. Cell Physiol Biochem. 2017;41(2):583-597. PubMed PMID: 28214878.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2. AU - Chen,Jing, AU - Xu,Yuejuan, AU - Tao,Leilei, AU - Pan,Yan, AU - Zhang,Kai, AU - Wang,Rui, AU - Chen,Long-Bang, AU - Chu,Xiaoyuan, Y1 - 2017/02/03/ PY - 2016/07/22/received PY - 2016/10/11/accepted PY - 2017/2/20/pubmed PY - 2017/6/7/medline PY - 2017/2/20/entrez KW - Chemoresistance KW - Enhancer of zeste homolog 2 KW - Epithelial-to-mesenchymal KW - Lung adenocarcinoma KW - microRNA-26a SP - 583 EP - 597 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 41 IS - 2 N2 - 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 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 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. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/28214878/MiRNA_26a_Contributes_to_the_Acquisition_of_Malignant_Behaviors_of_Doctaxel_Resistant_Lung_Adenocarcinoma_Cells_through_Targeting_EZH2_ L2 - https://www.karger.com?DOI=10.1159/000457879 DB - PRIME DP - Unbound Medicine ER -