RPL22L1作为候选分子标记驱动肺鳞癌转移发生的功能及相关机制

Lung squamous cell carcinoma is a common lung cancer subtype with high metastasis and recurrence rate and poor prognosis. Due to the lack of clear driving genes and corresponding targeted therapies, currently there is no significant breakthrough in treatment strategies for lung squamous cell carcinoma, so there is an urgent need for finding specific lung squamous cell cancer molecular markers to facilitate clinical diagnosis and treatment. Our previous study found that the like ribosomal protein RPL22L1 has specificity in lung squamous cell carcinoma and is highly correlated with the metastasis of squamous cell carcinoma of the lung. It regulates multiple steps of metastasis include cell migration and invasion, adhesion, induction of EMT, and the regulation of MAPKs pathway, suggesting that it played key role in cell migration regulation. In addition, the high amplification of RPL22L1 in lung squamous cell carcinoma also makes the gene more useful as a molecular marker for diagnosis and treatment. Therefore, the project intends to comprehensively and systematically study the contribution of RPL22L1 to the metastasis process of lung squamous cell carcinoma through clinical lung squamous cell carcinoma tissue samples, transgenic mouse models, and lung squamous cell carcinoma cell lines, clarify the molecular regulation mechanism, and prepare molecular probes, information such as pathology and prognosis was used to evaluate the accuracy of RPL22L1 in predicting metastasis of lung squamous cell carcinoma and to obtain its basis for metastasis molecular markers of lung squamous cell carcinoma. This study is of great significance for the molecular classification, metastasis prediction of lung squamous cell carcinoma, and targeted drug development.

肺鳞癌是一种常见的肺癌亚型，转移复发率高、预后差，由于缺少明确驱动基因和与之相应的靶向治疗，目前针对肺鳞癌的治疗方案始终没有显著突破，因此迫切需要寻找特异性的肺鳞癌分子标记以利于临床诊疗。我们前期研究发现类核糖体蛋白RPL22L1具有肺鳞癌表达特异性，与肺鳞癌转移高度相关，调控细胞迁移侵袭、黏附、诱导EMT以及上游MAPKs通路多个步骤，提示它处于细胞转移调控的上游关键位置。另外，RPL22L1在肺鳞癌组织中的高扩增也使得该基因更具作为诊治分子标志物的潜质。因此，本项目拟通过临床肺鳞癌组织样本、转基因小鼠模型以及肺鳞癌细胞系全面系统地研究RPL22L1对肺鳞癌转移过程中的贡献，明确分子调控机制，并制备分子探针，参照临床病理和预后等信息，评估RPL22L1预测肺鳞癌转移发生的准确性，获得其作为肺鳞癌转移分子标记的依据。该研究对于肺鳞癌分子分型、转移发生预测，以及靶向药物开发都具有重要意义。

肺鳞癌是一种常见的肺癌亚型，转移复发率高、预后差，由于缺少明确驱动基因和与之相应的靶向治疗，目前针对肺鳞癌的治疗方案始终没有显著突破，因此迫切需要寻找特异性的肺鳞癌分子标记以利于临床诊疗。前期研究发现类核糖体蛋白RPL22L1具有肺鳞癌表达特异性，且与肺鳞癌转移高度相关。本研究中进一步通过细胞模型、动物模型、临床样本充分探究RPL22L1对肺鳞癌转移相关性。研究发现RPL22L1在肺鳞癌中特异性高扩增、高表达，与肺鳞癌转移高度相关，调控细胞迁移侵袭、黏附、诱导EMT以及上游MAPKs-ERK、mTOR通路多个步骤，主要通过激活mTOR通路促进肺鳞癌细胞恶性表型进展。RPL22L1与肺鳞癌血管生成相关。拓展研究发现，RPL22L1在肝细胞癌、宫颈腺癌中同样具有重要的作用，通过ERK通路促进肝细胞癌、宫颈腺癌细胞恶性表型。