MicroRNA-1254 Suppresses Epithelial-Mesenchymal Transition by Upregulating c-Cellular Myelocytomatosis Oncogene (c-Myc) and Alleviates Drug Resistance in Lung Cancer

Abstract

Drug resistance is a huge challenge during the management of diseases. MicroRNA (miRNA) dys-regulation is known to contribute to tumor progression. Herein we aimed to explore miR-1254’s role in drug resistance in lung cancer. In the present study, we used Pabolizumab to treat drug-resistant and non-drug resistant lung cancer cells followed by analysis of miR-1254 expression by RT-qPCR, epithelial-mesenchymal transition (EMT) related protein and c-Myc expression by western blot, E-cadherin and N-cadherin level by immunofluorescence. Additionally, mouse model of lung cancer was treated with miR-1254 mimic and/or Pabolizumab to assess miR-1254’s role in lung cancerin vivo. Drug-resistant lung cancer cells exhibited significantly increased viability upon treatment with Pabolizumab with decreased miR-1254 expression. Besides, Pabolizumab upregulated E-caderin and downregulated N-cadherin. Importantly, miR-1254 bound to c-Myc in cancer cells. In the presence of miR-1254 mimic or siRNA (si)-c-Myc, the chemosensitivity of lung cancer cells was increased whereas miR-1254 inhibitor augmented cell resistance to Pabolizumab. Furthermore, the chemosensitivity induced by c-Myc could be depleted by miR-1254 inhibitor. Combined treatment of miR-1254 mimic and Pabolizumab significantly decreased tumor weight and volume, and reduced c-Myc level. In conclusion, miR-1254 might suppress EMT by inhibiting c-Myc expression in lung cancer and decrease drug resistance.