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LINC00511 drives invasive behavior in hepatocellular carcinoma by regulating exosome secretion and invadopodia formation
- Source :
- Journal of Experimental & Clinical Cancer Research : CR, Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-17 (2021)
- Publication Year :
- 2021
-
Abstract
- Background Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. Methods The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. Results We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. Conclusions Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression.
- Subjects :
- 0301 basic medicine
Cancer Research
Carcinoma, Hepatocellular
Carcinogenesis
Hepatocellular carcinoma
Invadopodia
medicine.disease_cause
Exosomes
Exosome
R-SNARE Proteins
03 medical and health sciences
medicine
Humans
Secretion
Neoplasm Invasiveness
Multivesicular body
Qc-SNARE Proteins
LncRNAs
RC254-282
030102 biochemistry & molecular biology
Chemistry
Research
Liver Neoplasms
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Qb-SNARE Proteins
Microvesicles
Long non-coding RNA
Cell biology
Gene Expression Regulation, Neoplastic
030104 developmental biology
Vesicle-associated membrane protein
Oncology
Tumor progression
Podosomes
Disease Progression
RNA, Long Noncoding
Subjects
Details
- ISSN :
- 17569966
- Volume :
- 40
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of experimentalclinical cancer research : CR
- Accession number :
- edsair.doi.dedup.....5306b70b85d50eea242f9c928fc79881