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


ABSTRACT:

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?ConclusionThe 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.

SUBMITTER: Xiong R 

PROVIDER: S-EPMC6938762 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Xiong Ran R   Sun Xiang-Xiang XX   Wu Han-Ran HR   Xu Guang-Wen GW   Wang Gao-Xiang GX   Sun Xiao-Hui XH   Xu Mei-Qing MQ   Xie Ming-Ran MR  

Thoracic cancer 20191127 1


<h4>Background</h4>To investigate the regulatory mechanism behind miR-34a-altered Axl levels in non-small-cell lung cancer (NSCLC) with gefitinib-acquired resistance.<h4>Methods</h4>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  ...[more]

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