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Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis
Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis
- Source :
- Cancer letters. 397
- Publication Year :
- 2016
-
Abstract
- Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumour progression. Therefore, understanding how CAFs communicate with hepatocellular carcinoma (HCC) is crucial for HCC therapy. Recently, exosomes have been considered an important “messenger” between cells. In this study, we performed microRNA (miRNA) sequencing of exosomes derived from CAFs and corresponding para-cancer fibroblasts (PAFs) of HCC patients. We found a significant reduction in the miR-320a level in CAF-derived exosomes. Using exogenous miRNAs, we demonstrated that stromal cells could transfer miRNA to HCC cells. In vitro and in vivo studies further revealed that miR-320a could function as an antitumour miRNA by binding to its direct downstream target PBX3 to suppress HCC cell proliferation, migration and metastasis. The miR-320a-PBX3 pathway inhibited tumour progression by suppressing the activation of the MAPK pathway, which could induce the epithelial–mesenchymal transition and upregulate cyclin-dependent kinase 2 (CDK2) and MMP2 expression to promote cell proliferation and metastasis. In xenograft experiments involving CAFs mixed with MHCC97-H cells, miR-320a overexpression in CAFs could inhibit tumourigenesis. Therefore, these data suggest that CAF-mediated HCC tumour progression is partially related to the loss of antitumour miR-320a in the exosomes of CAFs and that promoting the transfer of stromal cell-derived miR-320a might be a potential treatment option to overcome HCC progression.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Cancer Research
Stromal cell
MMP2
Carcinoma, Hepatocellular
Time Factors
Down-Regulation
Mice, Nude
Biology
Exosomes
Transfection
Metastasis
03 medical and health sciences
0302 clinical medicine
Cancer-Associated Fibroblasts
Cell Movement
Cell Line, Tumor
Proto-Oncogene Proteins
microRNA
Paracrine Communication
medicine
Animals
Humans
Neoplasm Invasiveness
Extracellular Signal-Regulated MAP Kinases
Cell Proliferation
Homeodomain Proteins
Cell growth
Cyclin-Dependent Kinase 2
Liver Neoplasms
medicine.disease
Microvesicles
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
Editorial
Oncology
030220 oncology & carcinogenesis
Cancer research
Signal Transduction
Subjects
Details
- ISSN :
- 18727980
- Volume :
- 397
- Database :
- OpenAIRE
- Journal :
- Cancer letters
- Accession number :
- edsair.doi.dedup.....0f2822778b159eb1213c62831cd829ec