microRNA-520a-3p inhibits proliferation and cancer stem cell phenotype by targeting HOXD8 in non-small cell lung cancer

摘要

Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigenesis, tumour recurrence and therapy resistance and microRNA is essential for the development of the biological traits of CSCs and the increased cells proliferation. Studying molecular mechanism of tumorigenesis, tumour recurrence and therapy resistance of lung cancer will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we found that miR-520a-3p expression is downregulated in NSCLC (non-small cell lung cancer) and SCLC (small cell lung cancer). miR-520a-3p can inhibit proliferation and cancer stem cell phenotype in NSCLC and SCLC cells. Overexpressing miR-520a-3p can degrade HOXD8 mRNA in NSCLC cells, but its overexpression cannot suppress HOXD8 in SCLC cells. HOXD8 protein is upregulated in NSCLC tissues and its overexpression can promote proliferation, formation of cancer stem cells, migration and invasion in NSCLC cells. MET amplification plays a pivotal role in gefitinib resistance in lung cancer. We found that miR-520a-3p can downregulate MET protein expression and HOXD8 can upregulate MET protein expression. Thus, we concluded that microRNA-520a-3p inhibits proliferation and cancer stem cell phenotype by targeting HOXD8 in NSCLC cells and restoration of microRNA-520a-3p might be a therapeutic strategy to reverse gefitinib resistance.