microRNA-1236-3p regulates DDP resistance in lung cancer cells

• Main Authors: Wang Zhigang, Liu Limei, Guo Xiaofeng, Guo Chunmei, Wang Wenxia
• Format: Article
• Language: English
• Published: De Gruyter 2019-01-01
• Series: Open Medicine
• Subjects: drug resistance; lung cancer; microrna-1236-3p; tpt1 gene; pim-3 signaling pathway
• Online Access: https://doi.org/10.1515/med-2019-0007

Lung cancer is a malignant tumor leading to the most cancer-related deaths worldwide. The treatment efficiency of lung cancer remains poor mainly due to chemotherapy drug resistance, including cisplatin. MicroRNAs (miRNAs) are closely related to chemotherapy resistance of tumor cells. Here, we illustrated the underlying mechanism of miR-1236-3p on the DDP resistance in lung cancer cells. In this study, we found that the expression level of miR-1236-3p was significantly decreased in lung cancer tissues and A549 cell line. In addition, the half maximal inhibitory concentration (IC50) of DDP in A549 cells was significantly lower than that in A549/DDP cells, while the expression level of miR-1236-3p was prominently down-regulated in A549/DDP cells. Combining the online tool TargetScan and a dual-luciferase reporter assay, tumor protein, translationally-controlled 1 (TPT1) was proved to be the direct target gene of miR-1236-3p. The MTT and flow cytometry assays demonstrated that up-regulation of miR-1236-3p could markedly inhibit A549/DDP cell proliferation but promote apoptosis, which could be significantly reversed by pcDNA3.1-TPT1 plasmids. Finally, we further demonstrated that miR-1235-3p could restrain the expression levels of TPT1, Pim-3, phosphate-Bcl-2-associated death promoter (p-BAD) and B-cell lymphoma-extra large (Bcl-XL) in A549/DDP cells, while the inhibition could be reversed by pcDNA3.1-TPT1 as well. In a word, our study demonstrated that miR-1236-3p could reverse DDP resistance by modulation of TPT1 gene and inhibition of Pim-3 signaling pathway in lung cancer cells.