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Archive > Volume 26 Issue 3 > 2019,26(3):266-272. DOI:10.3872/j.issn.1007-385X.2019.03.003 Prev Next
Basic Research
miR-103 targets PTEN to promote dasatinib resistance in lung cancer A549 cells via activating PI3K/AKT pathway
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Abstract:
[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) of A549/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 miR-103 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 and A549/DASA cells (P<0.01). Knockdown of miR-103 significantly inhibited the proliferation,invasion and EMT of A549/DASA cells (P<0.05 or P<0.01). Additionally, dual luciferase reporter gene assay confirmed that miR-103 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 in A549/DASA cells. 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.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 810600103), the Scientific Research Foundation of Education Department of Yunnan Province (No. 2013Y3002), and the Joint Special Fund for Science and Technology Planning of Yunnan Province (No. 2010CD150)
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