CircPVT1 contributes to chemotherapy resistance of lung adenocarcinoma through miR-145-5p/ABCC1 axis.

Recently, increasing studies have confirmed some circRNAs were involved in the genesis of chemotherapy resistance in almost all kinds of malignant tumors, including lung adenocarcinoma (LAD). Nevertheless, the function and mechanism of circPVT1 in regulating chemotherapy resistance of LAD has not been elucidated so far. The current study found circPVT1 was highly expressed in LAD, which expression was positively related to N stage and chemotherapy insensitivity (cisplatin and pemetrexed) of LAD patients, and it was an independent prognostic biomarker for LAD patients. The circPVT1 expression was up-regulated in LAD tissues and cell line (A549/DR) resistant to cisplatin and pemetrexed. CircPVT1 knockdown sensitized A549/DR cells to cisplatin and pemetrexed. RNA pull-down assay et al. confirmed circPVT1 acted as a ceRNA for miR-145-5p in A549/DR cells. In addition, miR-145-5p was lowly expressed in cisplatin and pemetrexed resistant LAD tissues and cell line, and its over-expression also sensitized A549/DR cells to cisplatin and pemetrexed. The luciferase reporter assay et al. proved ABCC1 was a target gene of miR-145-5p in A549/DR cells. Moreover, miR-145-5p enhancement partly restored the effecting of circPVT1 knockdown on chemotherapy resistance in A549/DR cells, miR-145-5p/ABCC1 pathway mediated chemotherapy resistance induced by circPVT1 knockdown in LAD cells. In conclusion, the high-expression of circPVT1 is related with the cisplatin and pemetrexed insensitivity of LAD patients, circPVT1 contributes to cisplatin and pemetrexed chemotherapy resistance through miR-145-5p/ABCC1 axis.