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Published on: February 8, 2020
CHRDL1 inhibits OSCC metastasis via MAPK signaling-mediated inhibition of MED29
Songkai Huang1, Junwei Zhang1, Yu Qiao2
1School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, China.
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.
Insights
The study reveals that MED29 promotes oral squamous cell carcinoma (OSCC) migration and invasion by facilitating epithelial-mesenchymal transition (EMT). CHRDL1 inhibits OSCC invasion and metastasis by suppressing MED29 and the MAPK signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The role of CHRDL1 in oral squamous cell carcinoma (OSCC) is largely unknown.
- Investigating novel mRNA molecules like CHRDL1 is crucial for understanding cancer progression.
Purpose of the Study:
- To elucidate the function of CHRDL1 in OSCC.
- To explore the relationship between CHRDL1 and MED29 in OSCC progression.
- To determine the underlying mechanisms of CHRDL1's action in OSCC.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and immunohistochemistry to assess MED29 expression in OSCC tissues and cell lines.
- Western Blot analysis for protein expression levels.
- In vitro assays (scratch, Transwell, wound healing, immunofluorescence) to evaluate MED29 and CHRDL1 effects on OSCC cell migration, invasion, and epithelial-mesenchymal transition (EMT).
- In vivo tail vein lung metastasis model in nude mice to assess CHRDL1's role in metastasis.
Main Results:
- MED29 expression is upregulated in OSCC tissues and cell lines, correlating with increased migration and invasion.
- MED29 overexpression promotes EMT, migration, and invasion in OSCC cells.
- Knockdown of MED29 inhibits EMT, migration, and invasion.
- CHRDL1 suppresses MED29 expression, thereby inhibiting EMT, invasion, and migration of OSCC cells.
- CHRDL1 inhibits OSCC cell migration by regulating MED29.
Conclusions:
- MED29 drives OSCC progression by promoting EMT, migration, and invasion.
- CHRDL1 acts as an inhibitor of OSCC invasion and metastasis.
- CHRDL1 exerts its inhibitory effects by suppressing MED29 expression, likely through the MAPK signaling pathway.
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