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Abstract Background CHRDL1 belongs to a novel class of mRNA molecules. Nonetheless, the specific biological functions and underlying mechanisms of CHRDL1 in oral squamous cell carcinoma (OSCC) remain largely unexplored. Methods RT-qPCR and immunohistochemical staining were employed to assess the mRNA and protein expression levels of the MED29 gene in clinical samples of OSCC. Additionally, RT-qPCR and Western Blot analyses were conducted to investigate the mRNA and protein expression levels of the MED29 gene specifically in OSCC. The impact of MED29 on epithelial-mesenchymal transition (EMT), invasion, and migration of OSCC was evaluated through scratch assay, transwell assay, and immunofluorescence staining. Furthermore, wound healing assay and Transwell assay were utilized to examine whether CHRDL1 influences the malignant behavior of OSCC by modulating MED29 in vitro. The regulatory role of CHRDL1 on MED29 was further elucidated in vivo through a tail vein lung metastasis model in nude mice. Results MED29 expression was elevated in tumor tissues of OSCC patients compared with adjacent cancer tissues. Moreover, in CAL27 and SCC25 cell lines, MED29 was upregulated and associated with increased cell migration and invasion abilities. Overexpression of MED29 facilitated EMT in OSCC cell lines, whereas knockdown of MED29 impeded EMT, resulting in diminished cell migration and invasion capacities. CHRDL1 exerted inhibitory effects on the expression of MED29, thereby suppressing EMT progression and consequently restraining the invasion and migration of OSCC cells. Furthermore, CHRDL1 mediated the inhibition of migration of OSCC cell lines to the OSCC through its regulation of MED29. Conclusions MED29 facilitated the epithelial-mesenchymal transition process in OSCC, thereby promoting migration and invasion. On the other hand, CHRDL1 exerted inhibitory effects on the invasion and metastasis of OSCC by suppressing MED29 through the inhibition of the MAPK signaling pathway.

BackgroundAccumulating evidence suggests that dysregulation of Chordin-like 1 (CHRDL1) is associated with malignant biological behaviors in multiple cancers. However, the exact function and molecular mechanism of CHRDL1 in oral squamous cell carcinoma (OSCC) remain unclear.MethodsThe expression levels of CHRDL1 in OSCC tissues and CAL27 cells were determined by RT-qPCR. Immunohistochemical staining was applied to detect CHRDL1 protein expression in sample tissues from OSCC patients. Gain of function and knockdown by lentivirus were further used to examine the effects of CHRDL1 on cell proliferation, migration, invasion, and adhesion in OSCC. Tail vein injection of CAL27 cells with dysregulated CHRDL1 expression was further used to examine the effect of CHRDL1 on lung colonization. RNA sequencing was performed to explore the molecular mechanisms of CHRDL1 that underlie the progression of OSCC.ResultsCHRDL1 was significantly downregulated in OSCC tissues and CAL27 cells compared to controls. CHRDL1 knockdown enhanced migration, invasion, adhesion, and EMT, but not proliferation, in CAL27 cells. Overexpression of CHRDL1 had the opposite effects. Moreover, CHRDL1 was proven to inhibit tumor metastasis in vivo. Mechanistically, MAPK signaling pathway components, including ERK1/2, p38, and JNK, were found to regulate the malignant biological behaviors of CAL27 cells.ConclusionsOur results suggest that CHRDL1 has an inhibitory effect on OSCC metastasis via the MAPK signaling pathway, which provides a new possible potential therapeutic target against OSCC.