Domvri K, Petanidis S, Anestakis D, Porpodis K, Bai C, Zarogoulidis P, Freitag L, Hohenforst-Schmidt W, Katopodi T (2020)
Publication Type: Journal article
Publication year: 2020
Book Volume: 11
Pages Range: 2847-2862
Journal Issue: 29
DOI: 10.18632/oncotarget.27675
Immunosuppressive chemoresistance is a major burden in lung cancer. Recent data reveal that long noncoding RNAs (lncRNAs) present in the lung tumor microenvironment are implicated in chemoresistant-related immune deregulation, and metastasis but their exact pathogenic role is still unknown. In this study, we investigate the role of lncRNA PCAT-1 in chemoresistant immunosuppression and its involvement in tumor stroma remodeling. Findings reveal PCAT-1 to regulate Kras-related lung chemoresistance through increased expression of the immunosuppressive micrornas miR-182/miR217 in lung tissues, thus promoting a pre-metastatic niche formation and a subsequent increase in lung metastatic burden. Elevated expression of PCAT-1 negative regulates p27/CDK6 expression by inducing G0/G1 cell cycle arrest through AMPK augmentation, contributing to a tumor-promoting status. Furthermore, PCAT-1 triggered fibroblast differentiation followed by CAF/myofibroblast secretion in TME triggering a CD133/SOX2-related stem cell phenotype. Subsequent PCAT-1 knockdown impaired CAF-mediated stromal activation, and reversed chemoresistance and tumor growth in vivo. Overall, these findings demonstrate the versatile roles of PCAT-1 in sustaining lung immunosuppressive neoplasia through tumor microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
APA:
Domvri, K., Petanidis, S., Anestakis, D., Porpodis, K., Bai, C., Zarogoulidis, P.,... Katopodi, T. (2020). Exosomal lncRNA PCAT-1 promotes Kras-associated chemoresistance via immunosuppressive miR-182/miR-217 signaling and p27/CDK6 regulation. Oncotarget, 11(29), 2847-2862. https://doi.org/10.18632/oncotarget.27675
MLA:
Domvri, Kalliopi, et al. "Exosomal lncRNA PCAT-1 promotes Kras-associated chemoresistance via immunosuppressive miR-182/miR-217 signaling and p27/CDK6 regulation." Oncotarget 11.29 (2020): 2847-2862.
BibTeX: Download