RAF1 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating LAGE1: an experimental research.
RAF1 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating LAGE1: an experimental research.
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RAF1通过调节LAGE 1促进下咽癌淋巴结转移的实验研究
DOI：
10.1186/s12967-022-03468-7
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发表时间：
2022-06-06
影响因子：
7.4
通讯作者：
Hu, Guohua
中科院分区：
文献类型：
--
作者：
Li, Yanshi;Pan, Min;Lu, Tao;Yu, Dan;Liu, Chuan;Wang, Zhihai;Hu, Guohua
关键词：
淋巴结转移是下咽癌独立的预后危险因素，也是治疗失败的主要原因。本研究旨在筛选下咽癌淋巴转移的差异表达基因，探讨下咽癌淋巴转移的机制。对患者的原发肿瘤进行转录组测序，通过生物信息学分析筛选差异基因。采用qRT-PCR、Western-blotting和免疫组化方法检测差异基因的表达，Kaplan-Meier法、log-rank检验和考克斯's检验分析其预后价值。接下来，FADU和SCC 15细胞系用于通过EdU、流式细胞术、伤口愈合和Transwell测定在体外和通过足垫异种移植小鼠模型在体内证明差异基因的功能。进行蛋白质组测序以筛选相关靶标。此外，还进行了体外和体内实验以验证淋巴转移的机制。转录组测序结果显示RAF1是淋巴结转移的显著差异基因，是独立的预后危险因素。体外实验表明，RAF1表达降低可抑制肿瘤细胞的增殖、迁移和侵袭，促进肿瘤细胞凋亡。体内实验表明RAF1能促进肿瘤生长和淋巴转移。蛋白质组测序和后续实验表明，LAGE 1可以促进肿瘤的发展和淋巴转移，并受到RAF 1的调控。提示RAF1可通过调控LAGE 1促进下咽癌淋巴结转移，为探索下咽癌新的治疗靶点提供依据，最终为下咽癌智能诊断和精确治疗的建立提供新的指导。
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.
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影响因子：
5.4
作者：
Kim YD;Park HR;Song MH;Shin DH;Lee CH;Lee MK;Lee SY
通讯作者：
Lee SY
影响因子：
8.8
作者：
Dyrskjot, L.;Zieger, K.;Lildal, T. Kissow;Reinert, T.;Gruselle, O.;Coche, T.;Borre, M.;Orntoft, T. F.
通讯作者：
Orntoft, T. F.
影响因子：
3.1
作者：
Li, Yanshi;Lu, Tao;Hu, Guohua
通讯作者：
Hu, Guohua
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
6.4
作者：
Gangkofner, Dominik S.;Holzinger, Dana;Laban, Simon
通讯作者：
Laban, Simon