RAF1 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating LAGE1: an experimental research

• Published in: Journal of translational medicine Vol. 20; no. 1; pp. 255 - 23
• Main Authors: Li, Yanshi, Pan, Min, Lu, Tao, Yu, Dan, Liu, Chuan, Wang, Zhihai, Hu, Guohua
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.06.2022; BioMed Central; BMC
• Subjects: Analysis; Animals; Antigens; Apoptosis; Bioinformatics; Cancer therapies; Carcinoma, Squamous Cell - pathology; Care and treatment; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Chemotherapy; Cytokines; Diagnosis; Drug resistance; Experimental research; Flow cytometry; Gene Expression Regulation, Neoplastic; Genes; Head and neck cancer; Hospitals; Humans; Hypopharyngeal carcinoma; Hypopharyngeal Neoplasms - genetics; Immunotherapy; Kinases; LAGE1; Lymphatic Metastasis; Lymphatic system; Medical prognosis; Metastases; Metastasis; Mice; Polymerase chain reaction; Prevention; Proteins; Proteomic sequencing; Proteomics; Radiation therapy; RAF1; Risk factors; T cell receptors; Testing; Therapeutic targets; Throat cancer; Transcriptome sequencing; Transcriptomes; Tumor cells; Tumors; Wound healing; Xenografts; China; Lymphatic metastasis; Transcriptome sequencing; LAGE1; Proteomic sequencing; RAF1; Hypopharyngeal carcinoma
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-022-03468-7

Lymphatic metastasis was an independent prognostic risk factor for hypopharyngeal carcinoma and was the main cause of treatment failure. The purpose of this study was to screen the differential genes and investigate the mechanism of lymphatic metastasis in hypopharyngeal carcinoma. Transcriptome sequencing was performed on primary tumors of patients, and differential genes were screened by bioinformatics analysis. The expression of differential genes was verified by qRT-PCR, western-blotting and immunohistochemical, and prognostic value was analyzed by Kaplan-Meier and log-rank test and Cox's test. Next, FADU and SCC15 cell lines were used to demonstrate the function of differential genes both in vitro by EdU, Flow cytometry, Wound Healing and Transwell assays and in vivo by a foot-pad xenograft mice model. Proteomic sequencing was performed to screen relevant targets. In addition, in vitro and in vivo experiments were conducted to verify the mechanism of lymphatic metastasis. Results of transcriptome sequencing showed that RAF1 was a significantly differential gene in lymphatic metastasis and was an independent prognostic risk factor. In vitro experiments suggested that decreased expression of RAF1 could inhibit proliferation, migration and invasion of tumor cells and promote apoptosis. In vivo experiments indicated that RAF1 could promote tumor growth and lymphatic metastasis. Proteomic sequencing and subsequent experiments suggested that LAGE1 could promote development of tumor and lymphatic metastasis, and was regulated by RAF1. It suggests that RAF1 can promote lymphatic metastasis of hypopharyngeal carcinoma by regulating LAGE1, and provide a basis for the exploring of novel therapeutic target and ultimately provide new guidance for the establishment of intelligent diagnosis and precise treatment of hypopharyngeal carcinoma.