Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 6/2017

11.03.2017 | Original Article – Cancer Research

Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression

verfasst von: Lei Pan, Wei Liang, Min Fu, Zhen-hua Huang, Xia Li, Wen Zhang, Peng Zhang, Hui Qian, Peng-cheng Jiang, Wen-rong Xu, Xu Zhang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

ZFAS1 is a newly identified long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes mediate cellular communications in cancer by transmitting active molecules. The presence of ZFAS1 in the circulating exosomes and the roles of exosomal ZFAS1 in gastric cancer (GC) remains unknown. The aim of this study was to investigate the potential roles of exosomal ZFAS1 in GC.

Methods

The expression of ZFAS1 was examined in the tumor tissues, serum samples, serum exosomes of GC patients and cell lines using qRT-PCR. The correlation between ZFAS1 expression and the clinicopathological characteristics was analyzed. The characteristics of exosomes were identified using transmission electron microscope (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. The biological roles of ZFAS1 in GC cell growth and mobility were investigated using cell counting, cell colony formation, and transwell migration assay. The potential mechanism of ZFAS1 was demonstrated using flow cytometry, western blot, and qRT-PCR.

Results

ZFAS1 expression was elevated in GC cells, tumor tissues, serum and serum exosomes of GC patients. The increased ZFAS1 expression was significantly correlated with lymphatic metastasis and TNM stage. ZFAS1 knockdown inhibited the proliferation and migration of GC cells by suppressing cell cycle progression, inducing apoptosis, and inhibiting epithelial-mesenchymal transition (EMT). On the contrary, ZFAS1 overexpression promoted the proliferation and migration of GC cells. Moreover, ZFAS1 was present in exosomes and could be transmitted by exosomes to enhance GC cell proliferation and migration.

Conclusion

ZFAS1 could be delivered by exosomes to promote GC progression, which suggests that ZFAS1 may serve as a potential diagnostic and prognostic biomarker for GC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat Chun HW, Hong R (2016) Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma. Oncol Lett 12:1753–1762 doi:10.3892/ol.2016.4884 PubMedPubMedCentral Chun HW, Hong R (2016) Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma. Oncol Lett 12:1753–1762 doi:10.​3892/​ol.​2016.​4884 PubMedPubMedCentral
Zurück zum Zitat Dong L et al (2016) Circulating long RNAs in serum extracellular vesicles: Their characterization and potential application as biomarkers for diagnosis of colorectal cancer. Cancer Epidemiol Biomarkers Prev 25:1158–1166. doi:10.1158/1055-9965.EPI-16-0006 CrossRefPubMed Dong L et al (2016) Circulating long RNAs in serum extracellular vesicles: Their characterization and potential application as biomarkers for diagnosis of colorectal cancer. Cancer Epidemiol Biomarkers Prev 25:1158–1166. doi:10.​1158/​1055-9965.​EPI-16-0006 CrossRefPubMed
Zurück zum Zitat Karlsson O, Rodosthenous RS, Jara C, Brennan KJ, Wright RO, Baccarelli AA, Wright RJ (2016) Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development Epigenetics:0 doi:10.1080/15592294.2016.1216285 Karlsson O, Rodosthenous RS, Jara C, Brennan KJ, Wright RO, Baccarelli AA, Wright RJ (2016) Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development Epigenetics:0 doi:10.​1080/​15592294.​2016.​1216285
Zurück zum Zitat Liu H, Lv Z, Guo E (2015) Knockdown of long noncoding RNA SPRY4-IT1 suppresses glioma cell proliferation, metastasis and epithelial-mesenchymal transition. Int J Clin Exp Pathol 8:9140–9146PubMedPubMedCentral Liu H, Lv Z, Guo E (2015) Knockdown of long noncoding RNA SPRY4-IT1 suppresses glioma cell proliferation, metastasis and epithelial-mesenchymal transition. Int J Clin Exp Pathol 8:9140–9146PubMedPubMedCentral
Zurück zum Zitat Lu M, Liu Z, Li B, Wang G, Li D, Zhu Y (2016) The high expression of long non-coding RNA PANDAR indicates a poor prognosis for colorectal cancer and promotes metastasis by EMT pathway. J Cancer Res Clin Oncol. doi:10.1007/s00432-016-2252-y PubMedCentral Lu M, Liu Z, Li B, Wang G, Li D, Zhu Y (2016) The high expression of long non-coding RNA PANDAR indicates a poor prognosis for colorectal cancer and promotes metastasis by EMT pathway. J Cancer Res Clin Oncol. doi:10.​1007/​s00432-016-2252-y PubMedCentral
Zurück zum Zitat Nie F et al (2016) Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression. Oncotarget. doi:10.18632/oncotarget.9611 Nie F et al (2016) Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression. Oncotarget. doi:10.​18632/​oncotarget.​9611
Zurück zum Zitat Shao Y et al (2016) LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer. Oncotarget. doi:10.18632/oncotarget.9336 Shao Y et al (2016) LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer. Oncotarget. doi:10.​18632/​oncotarget.​9336
Zurück zum Zitat Thorenoor N, Faltejskova-Vychytilova P, Hombach S, Mlcochova J, Kretz M, Svoboda M, Slaby O (2016) Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer. Oncotarget 7:622–637. doi:10.18632/oncotarget.5807 PubMed Thorenoor N, Faltejskova-Vychytilova P, Hombach S, Mlcochova J, Kretz M, Svoboda M, Slaby O (2016) Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer. Oncotarget 7:622–637. doi:10.​18632/​oncotarget.​5807 PubMed
Zurück zum Zitat Wu L et al (2016) Exosomes derived from gastric cancer cells activate NF-kappaB pathway in macrophages to promote cancer progression. Tumour Biol. doi:10.1007/s13277-016-5071-5 Wu L et al (2016) Exosomes derived from gastric cancer cells activate NF-kappaB pathway in macrophages to promote cancer progression. Tumour Biol. doi:10.​1007/​s13277-016-5071-5
Zurück zum Zitat Zhou H et al (2016) Increased expression of long-noncoding RNA ZFAS1 is associated with epithelial mesenchymal transition of gastric cancer. Aging. doi:10.18632/aging.101048 Zhou H et al (2016) Increased expression of long-noncoding RNA ZFAS1 is associated with epithelial mesenchymal transition of gastric cancer. Aging. doi:10.​18632/​aging.​101048
Metadaten
Titel
Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression
verfasst von
Lei Pan
Wei Liang
Min Fu
Zhen-hua Huang
Xia Li
Wen Zhang
Peng Zhang
Hui Qian
Peng-cheng Jiang
Wen-rong Xu
Xu Zhang
Publikationsdatum
11.03.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2017
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-017-2361-2

Weitere Artikel der Ausgabe 6/2017

Journal of Cancer Research and Clinical Oncology 6/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.