A novel tumour suppressor lncRNA F630028O10Rik inhibits lung cancer angiogenesis by regulating miR-223-3p

Abstract

Lung cancer is the world's leading cause of cancer-related morbidity and mortality despite advances in surgery, chemotherapy and immunotherapy; thus, there is an urgent need to find new molecules to develop novel treatment strategies. Although ncRNAs were found to account for 98% transcripts, the number of lncRNAs with distinct function in lung cancer is extremely limited. We previously demonstrated that Plasmodium infection inhibits tumour growth and metastasis, but the exact mechanisms involved have not been fully understood. In this study, we carried out RNA sequencing (RNA-Seq) of tumour tissues isolated from LLC tumour-bearing mice treated with either Plasmodium yoelli (Py)-infected red blood cells or uninfected red blood cells. We found that F630028O10Rik (abbreviated as F63) is a novel lncRNA that was significantly up-regulated in tumours isolated from mice treated with Py-infected red blood cells compared to the control. By using gene silencing technique, F63 was found to inhibit both tumour Vascular Endothelial Growth Factor A (VEGFA) secretion and endothelial cells clone formation, migration, invasion and tube formation. Injection of cholesterol-modified siRNA-F63 into mice tumour tissues produced a significant increase in tumour volume, blood vessel formation and angiogenesis 17 days after injection. We further showed that inhibiting miR-223-3p results in the down-regulation of VEGFA and VEGFR2 which are vital molecules for angiogenesis. These results reveal that F63 inhibit tumour growth and progression by modulating tumour angiogenesis suggesting F63 can be a novel lncRNA with great potential as a candidate molecule for gene therapy in lung cancer.

Keywords: F630028O10Rik; LncRNA; angiogenesis; lung cancer; miR-223-3p.