Small protein DDX11-AS1-ORF encoded by lncRNA DDX11-AS1 promotes colorectal cancer progression through VEGFA-activated p38-MAPK pathway.

This study aims to investigate the expression, function, and mechanism of action of the small protein DDX11 antisense RNA 1 - open reading frame (DDX11-AS1-ORF), encoded by the long non-coding RNA (lncRNA) DDX11 antisense RNA 1 (DDX11-AS1), in the progression of colorectal cancer (CRC). The expression levels of DDX11-AS1 were assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in 10 pairs of colorectal cancer tissues and corresponding non-tumor tissues. Functional evaluations of DDX11-AS1 and DDX11-AS1-ORF were conducted using cell counting kit-8 (CCK8) assays, colony formation assays, Transwell migration assays, and in vitro tube formation assays. The coding potential of DDX11-AS1 was validated by western blot and immunofluorescence. The activation of the p38 mitogen-activated protein kinase (p38-MAPK) pathway by DDX11-AS1-ORF through VEGFA was analyzed using western blot. The results showed that DDX11-AS1 was significantly upregulated in colorectal cancer tissues and cells, promoting cancer cell proliferation, migration, and angiogenesis. DDX11-AS1 translated into a functional small protein, DDX11-AS1-ORF, which independently enhanced the malignant behaviors of tumor cells. DDX11-AS1-ORF promoted colorectal cancer progression by activating the p38-MAPK signaling pathway through Vascular Endothelial Growth Factor A (VEGFA). The critical role of the p38-MAPK pathway in DDX11-AS1-ORF mediated tumor promotion was confirmed using the p38-MAPK pathway inhibitor SB203580. In conclusion, the small protein DDX11-AS1-ORF, encoded by DDX11-AS1, plays a crucial role in the development of colorectal cancer by promoting tumor proliferation, migration, and angiogenesis through the activation of VEGFA and the p38-MAPK signaling pathway. These findings provide a novel potential target for molecular targeted therapy in colorectal cancer.