Exosome‐transmitted circ_MMP2 promotes hepatocellular carcinoma metastasis by upregulating MMP2

Autor: Ming-Tai Gao, Fang Zhang, Dongqin Chen, Mianli Li, Li Jin, Linghui Xiao, Deng-Rui Liu, Hong-Xia Kang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Cancer Research
MMP2
Exosomes
medicine.disease_cause
Metastasis
0302 clinical medicine
Neoplasm Metastasis
circ_MMP2
HCC
Research Articles
Liver Neoplasms
General Medicine
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Up-Regulation
Gene Expression Regulation
Neoplastic
Liver
Oncology
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Matrix Metalloproteinase 2
Molecular Medicine
Research Article
Carcinoma
Hepatocellular
Mice
Nude
Biology
Models
Biological
Exosome
lcsh:RC254-282
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
Genetics
medicine
Animals
Humans
exosome
metastasis
Gene Silencing
Base Sequence
RNA
Circular
medicine.disease
Microvesicles
digestive system diseases
MicroRNAs
030104 developmental biology
Tumor progression
Cancer research
Carcinogenesis
Zdroj: Molecular Oncology, Vol 14, Iss 6, Pp 1365-1380 (2020)
Molecular Oncology
ISSN: 1574-7891
1878-0261
Popis: Exosomes released by tumor cells have been recently identified as important determinants of tumor progression. They often carry circular RNAs that are differentially expressed in tumors and may regulate tumorigenesis and metastasis. Here, we showed that supernatant of 97H hepatocellular carcinoma (HCC) cell line could promote metastasis in L02 human liver cells and HCC cell lines. Moreover, we determined that circ_MMP2 (has_circ_0039411) could be delivered by 97H‐ or LM3 cell‐derived exosomes to L02 and HepG2 cell cultures. High expression of circ_MMP2 led to the upregulation of its host gene matrix metallopeptidase 2 (MMP2) via the sponging of miR‐136‐5p. Rescue assays demonstrated that miR‐136‐5p and MMP2 were two essential participants in HCC metastasis. Finally, high level of circ_MMP2 or MMP2, as well as low level of miR‐136‐5p, was correlated with low overall survival of HCC patients. Our study highlights a novel molecular pathway in HCC cell‐derived exosomes.
97H and LM3 cell line cocultured together had strong metastasis capacity. They released exosomes to produce circ_MMP2 to sponge miR‐136‐5p by enhancing MMP2 to accelerate the process hepatocellular cancinoma.
Databáze: OpenAIRE
Externí odkaz: