Oncotarget Volume 11, Issue 29 reported that Immunosuppressive chemoresistance is a major burden in lung cancer.
Recent data reveal that long noncoding RNAs present in the lung tumour microenvironment are implicated in chemoresistant-related immune deregulation, and metastasis but their exact pathogenic role is still unknown.
In this study, the Oncotarget authors investigate the role of lncRNA PCAT-1 in chemoresistant immunosuppression and its involvement in tumour 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.
Subsequent PCAT-1 knockdown impaired CAF-mediated stromal activation, and reversed chemoresistance and tumour growth in vivo.
Overall, these findings demonstrate the versatile roles of PCAT-1 in sustaining lung immunosuppressive neoplasia through tumour microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumours.
"Overall, these findings demonstrate the versatile roles of PCAT-1 in sustaining lung immunosuppressive neoplasia through tumour microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumours"
Dr. Savvas Petanidis from The Aristotle University of Thessaloniki as well as the I.M. Sechenov First Moscow State Medical University said, "Lung cancer remains the leading cause of cancer-related deaths and despite extensive research efforts, the survival rate of lung cancer patients remains significantly low."
Emerging evidence indicates that lncRNAs present in the lung tumour microenvironment promote tumour growth through cancer cell remodeling that favors immunosuppressive metastasis.
These decisive tumour propagating effects of lncRNA permit tumour cells to bypass immune surveillance and reduce T-cell infiltration into tumour, limiting the clinical benefits of immune checkpoint therapies.
Fibroblasts which play a key role in this mechanism, constitute most of the stromal cells in tumour tissues, secrete a wide spectrum of chemokines or cytokines to the tumour microenvironment, thus promoting growth, invasion, angiogenesis.
Furthermore, fibroblast-derived exosomes induce cancer stem cell expression that contributes to altered tumour metabolism and emergence of chemoresistance in tumour microenvironment.
In this study the authors characterise for the first time the role of lncRNA PCAT-1 in Kras-related lung chemoresistance and its role in tumour stroma remodeling via immunosuppressive miR-182/miR217 expression and fibroblast differentiation.
The Petanidis Research Team concluded in their Oncotarget Research Paper that "our findings reveal for the first time the key role of lncRNA PCAT-1 in regulating Kras-related lung chemoresistance and its role in tumour stroma remodeling via immunosuppressive miR-182/miR217 expression.
Aberrant expression of PCAT-1 in the tumour microenvironment triggers fibroblast differentiation which negative regulates p27/CDK6 by inducing G0/G1 cell cycle arrest and AMPK augmentation, contributing to a tumour-favoring metabolic status.
Our findings highlight the crucial relationship between CAFs and PCAT-1 which establish a CD133/SOX2-related stem cell phenotype and promote cancer cell chemoresistance.
Decoding these molecular mechanisms and their impact in chemotherapy induction is essential for introducing novel immune-based strategies to restore and maintain antitumour immunity in chemoresistant metastasis."
Source: IMPACT JOURNALS LLC
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