Mechanism research of miR-34a regulates Axl in non-small-cell lung cancer with gefitinib-acquired resistance.

Autor: Xiong R; Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Sun XX; Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Wu HR; Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Xu GW; Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Wang GX; Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Sun XH; Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Xu MQ; Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China., Xie MR; Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Jazyk: angličtina
Zdroj: Thoracic cancer [Thorac Cancer] 2020 Jan; Vol. 11 (1), pp. 156-165. Date of Electronic Publication: 2019 Nov 27.
DOI: 10.1111/1759-7714.13258
Abstrakt: Background: To investigate the regulatory mechanism behind miR-34a-altered Axl levels in non-small-cell lung cancer (NSCLC) with gefitinib-acquired resistance.
Methods: The expression of miR-34a, Axl, Gas6 and related downstream signaling proteins in the EGFR mutant NSCLC cell lines were determined by qRT-PCR and Western blot; PC9-Gef-miR-34a and HCC827-Gef-miR-34a cells were established by transfecting the parent cells with a miR-34a overexpressing virus, then the expression of Axl, Gas6 and the downstream channel-related proteins were also compared in PC9-Gef-miR-34a and HCC827-Gef-miR-34a and drug-resistant strains. The survival rate of the cells were measured by CCK8 assay. A luciferase reporter detected whether Axl was the target of miR-34a. Finally, a tumor-bearing nude mouse model was established to verify the relationship between the expression of miR-34a, Axl and Gas6 mRNA in vivo.
Results: The expression levels of Axl mRNA and protein, Gas6 mRNA and protein, and related downstream proteins in PC9-Gef and HCC827-Gef cell lines were higher than those in PC9 and HCC827 parental cell lines, while the expression of miR-34a was lower than it was in the parental cell lines (P < 0.05). The expression of Axl mRNA and protein, Gas6 mRNA and protein, and related downstream signaling proteins in PC9-Gef and HCC827-Gef cell lines was higher than the expression in PC9-Gef-miR-34a and HCC827-Gef-miR-34a cells, which overexpressed miR-34a (P < 0.05).
Conclusion: The miR-34a regulation of Axl plays an important role in NSCLC-acquired gefitinib resistance, and their expression is inversely correlated, which suggests that they can be used as prognostic markers or potential therapeutic targets for NSCLC.
(© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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