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

Autor: Xiaoping Zhu, Yanfeng Chen, Menglong Zhong, Nina Wang, Limei Qin, Zhili Li, Xiaoping Chen, Qiang Fu, Chunquan Ma, Dickson Adah, Li Qin
Rok vydání: 2020
Předmět:
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Lung Neoplasms
F630028O10Rik
Transcription
Genetic
Angiogenesis
medicine.medical_treatment
Biology
Models
Biological
Metastasis
angiogenesis
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
medicine
Animals
Gene silencing
Genes
Tumor Suppressor
Lung cancer
miR‐223‐3p
Tube formation
Neovascularization
Pathologic
Endothelial Cells
Original Articles
Cell Biology
Immunotherapy
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
LncRNA
Gene Expression Regulation
Neoplastic
Mice
Inbred C57BL
Disease Models
Animal
MicroRNAs
lung cancer
Vascular endothelial growth factor A
030104 developmental biology
medicine.anatomical_structure
Protein Biosynthesis
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
RNA
Long Noncoding
Original Article
Blood vessel
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.15044
Popis: 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.
Databáze: OpenAIRE
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