CHRDL1 通过 MAPK 信号通路介导抑制 MED29 抑制 OSCC 转移。
CHRDL1 inhibits OSCC metastasis via MAPK signaling-mediated inhibition of MED29.
机构信息
School 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.
Department of Stomatology, The Seventh Affiliated Hospital, Sun Yat-Ssen University, Shenzhen, 518000, Guangdong, China.
出版信息
Mol Med. 2024 Oct 26;30(1):187. doi: 10.1186/s10020-024-00956-y.
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.
背景
CHRDL1 属于一类新型的 mRNA 分子。然而，CHRDL1 在口腔鳞状细胞癌（OSCC）中的具体生物学功能和潜在机制仍在很大程度上未被探索。
方法
采用 RT-qPCR 和免疫组织化学染色法评估 MED29 基因在 OSCC 临床样本中的 mRNA 和蛋白表达水平。此外，还进行了 RT-qPCR 和 Western Blot 分析，以专门研究 MED29 基因在 OSCC 中的 mRNA 和蛋白表达水平。通过划痕实验、Transwell 实验和免疫荧光染色评估 MED29 对 OSCC 上皮-间充质转化（EMT）、侵袭和迁移的影响。此外，通过划痕实验和 Transwell 实验检测了 CHRDL1 是否通过调节 MED29 在体外影响 OSCC 的恶性行为。通过裸鼠尾静脉肺转移模型进一步在体内阐明了 CHRDL1 对 MED29 的调节作用。
结果
与相邻癌组织相比，OSCC 患者的肿瘤组织中 MED29 的表达升高。此外，在 CAL27 和 SCC25 细胞系中，MED29 上调并与细胞迁移和侵袭能力增强相关。OSCC 细胞系中 MED29 的过表达促进 EMT，而 MED29 的敲低则抑制 EMT，导致细胞迁移和侵袭能力降低。CHRDL1 对 MED29 的表达具有抑制作用，从而抑制 EMT 进展，进而抑制 OSCC 细胞的侵袭和迁移。此外，CHRDL1 通过调节 MED29 介导 OSCC 细胞系迁移的抑制。
结论
MED29 促进了 OSCC 中的上皮-间充质转化过程，从而促进了迁移和侵袭。另一方面，CHRDL1 通过抑制 MAPK 信号通路抑制 MED29 的表达，对 OSCC 的侵袭和转移发挥抑制作用。
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