PURPOSE: Long non-coding RNA (lncRNA) prostate cancer-associated transcripts 1 (PCAT1) is a noticeable lncRNA involved in the tumorigenesis of various cancers. Nowadays, the biological function of PCAT1 on the stemness of non-small cell lung cancer (NSCLC) is still unclear. Our purpose was to explore the molecular mechanism of PCAT1 and its target protein in advanced NSCLC. METHODS: The levels of PCAT1 and Fyn-related kinase (FRK) in NSCLC tissues and cell lines were evaluated by quantitative polymerase chain reaction (qPCR). The log-rank test was applied to evaluate the role of high PCAT1 levels in shortening the overall survival of NSCLC patients. Chi-square test was to assess the relation between PCAT1 expression and clinicopathological features of NSCLC patients. CCK8 assay tested the cell proliferation of NSCLC cells with PCAT1 overexpression. The underlying regulatory mechanism between PCAT1 and Fyn-related kinase (FRK) was predicted by bioinformatics and verified by RNA transfection, qPCR, and western blotting. Chromatin immunoprecipitation (ChIP) assay was done to examine the relation between GATA binding protein 6 (GATA6) and the PACT1 gene. Mice xenografts were applied to examine the function of PACT1 on NSCLC development in vivo. RESULTS: PCAT1 was aberrantly elevated in tissues from patients with NSCLC. High levels of PCAT1 expression were more likely to present in patients with late-stage, positive CD133, and inferior overall survival. PCAT1 knockdown reduced cell proliferation, stem cell properties (Sox2 and Nanog expression) of H226 and A549 cells in vitro, and repressed tumor development in vivo. Furthermore, FRK in NSCLC cells was downregulated by silencing PCAT1. The tissue level of FRK was positively correlated with PCAT1 expression in patients with NSCLC. Furthermore, GATA6 was found to be promoter of PCAT1 and increased PCAT1 levels in NSCLC cells. CONCLUSIONS: GATA6/PCAT1 may markedly maintain the stemness of NSCLC, resulting in late TNM stage and poor survival. These findings suggest that the GATA6-PCAT1-FRK axis may be a useful target for intervention in NSCLC.
PURPOSE: Long non-coding RNA (lncRNA) prostate cancer-associated transcripts 1 (PCAT1) is a noticeable lncRNA involved in the tumorigenesis of various cancers. Nowadays, the biological function of PCAT1 on the stemness of non-small cell lung cancer (NSCLC) is still unclear. Our purpose was to explore the molecular mechanism of PCAT1 and its target protein in advanced NSCLC. METHODS: The levels of PCAT1 and Fyn-related kinase (FRK) in NSCLC tissues and cell lines were evaluated by quantitative polymerase chain reaction (qPCR). The log-rank test was applied to evaluate the role of high PCAT1 levels in shortening the overall survival of NSCLCpatients. Chi-square test was to assess the relation between PCAT1 expression and clinicopathological features of NSCLCpatients. CCK8 assay tested the cell proliferation of NSCLC cells with PCAT1 overexpression. The underlying regulatory mechanism between PCAT1 and Fyn-related kinase (FRK) was predicted by bioinformatics and verified by RNA transfection, qPCR, and western blotting. Chromatin immunoprecipitation (ChIP) assay was done to examine the relation between GATA binding protein 6 (GATA6) and the PACT1 gene. Mice xenografts were applied to examine the function of PACT1 on NSCLC development in vivo. RESULTS:PCAT1 was aberrantly elevated in tissues from patients with NSCLC. High levels of PCAT1 expression were more likely to present in patients with late-stage, positive CD133, and inferior overall survival. PCAT1 knockdown reduced cell proliferation, stem cell properties (Sox2 and Nanog expression) of H226 and A549 cells in vitro, and repressed tumor development in vivo. Furthermore, FRK in NSCLC cells was downregulated by silencing PCAT1. The tissue level of FRK was positively correlated with PCAT1 expression in patients with NSCLC. Furthermore, GATA6 was found to be promoter of PCAT1 and increased PCAT1 levels in NSCLC cells. CONCLUSIONS:GATA6/PCAT1 may markedly maintain the stemness of NSCLC, resulting in late TNM stage and poor survival. These findings suggest that the GATA6-PCAT1-FRK axis may be a useful target for intervention in NSCLC.
Authors: Joakin O Mori; Jason White; Isra Elhussin; Babatunde M Duduyemi; Balasubramanyam Karanam; Clayton Yates; Honghe Wang Journal: Front Oncol Date: 2022-08-10 Impact factor: 5.738