miR-103 targets PTEN to promote dasatinib resistance in lung cancer A549 cells via activating PI3K/AKT pathway
10.3872/j.issn.1007-385x.2019.03.003
- VernacularTitle:miR-103靶向PTEN并激活PI3K/AKT通路促进肺癌细胞A549对达沙 替尼耐药
- Author:
SUN Hongwen
1
;
ZHOU Xiaoting
2
;
BAO Yanan
1
;
XIONG Guosheng
1
;
CUI Yue
1
;
ZHOU Hua
3
Author Information
1. Department of Thoracic Surgery，the First Affiliated Hospital of Kunming Medical University,
2. The Second Clinical Medical College of Fujian Medical University
3. Department of Oncology Radiotherapy, the First Affiliated Hospital of Kunming Medical University,
- Publication Type:Journal Article
- Keywords:
lung cancer;
A549 cell;
dasatinib (DASA);
miR-103;
PTEN;
PI3K/AKT
- From:
Chinese Journal of Cancer Biotherapy
2019;26(3):266-272
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the mechanism of miR-103 targeting PTEN (gene of phosphate and tension homology deleted on chromsome ten) and activating PI3K/AKT signaling pathway to promote dasatinib (DASA) resistance in lung cancer cells. Methods: DASA-resistant tissues and non-resistant tissues (35 samples for each) from patients treated in Department of Thoracic Surgery, the First Affiliated Hospital of Kunming Medical University from April 2014 to January 2018 were collected for this study. Expression of miR-103 was detected in DASA-resistant tissues and cell lines of lung cancer by quantitative Real-time polymerase chain reaction (qPCR). The effect of miR-103 knock-down on the proliferation, invasion and epithelial mesenchymal transition (EMT) ofA549/DASA cells were measured by CCK-8 assay, Transwell and Wb, respectively. Subsequently, the dual luciferase reporter gene assay was used to verify whether PTEN was a target gene of miR-103. CCK-8, Transwell and Wb assay were further used to investigate the effect of miR103 on malignant biological behaviors of A549/DASA cells via regulating PTEN-PI3K/AKT signaling pathway. Results: miR-103 was highly expressed in DASA-resistant tissues andA549/DASAcells (P<0.01). Knockdown of miR-103 significantly inhibited the proliferation, invasion and EMT ofA549/DASAcells (P<0.05 or P<0.01).Additionally, dual luciferase reporter gene assay confirmed that miR103 directly targeted PTEN and down-regulated its expression (P<0.01). Mechanistically, over-expression of miR-103 targeted and down-regulated PTEN to promote cell viability, invasion and EMT via activating PI3K/AKT pathway (P<0.05 or P<0.01), and further up-regulated the DASA-resistance inA549/DASAcells. Conclusion: miR-103/PTEN/PI3K/AKT signaling pathway plays a certain role in regulating DASA resistance of lung cancer, and knockdown of miR-103 expression may reverse the resistance of A549/DASA cells to DASA.
- Full text:20190303.pdf
