UVB辐射诱导的MALAT1-Importin7-HIF1α调控轴在皮肤鳞癌进程中的作用机制研究

电磁辐射中的UVB辐射是皮肤鳞癌的重要诱因。非编码RNA MALAT1在肿瘤进程中的作用机制是近年来的研究热点。.我们前期工作证实：MALAT1在UVB照射后的角质形成细胞HaCaT中表达增高，在皮肤鳞癌组织、细胞中高表达。它能促进细胞恶性生物学行为和皮下移植瘤生长、调控IPO7表达。.根据生物信息学预测及预实验结果提出科学假设：MALAT1通过调控IPO7的表达影响其转运转录因子HIF1α入核，促进皮肤鳞癌进程。据此，本项目主要研究内容为：⑴UVB暴露后MALAT1调控IPO7表达，促进HIF1α入核并提高其转录活性，诱导皮肤鳞癌发生发展。⑵MALAT1-IPO7-HIF1α调控轴影响皮肤鳞癌进程的分子机制。.本项目从MALAT1调控输入蛋白表达影响转录因子入核角度为lncRNA在肿瘤进程中的调控作用研究提供新视野，对揭示UVB诱导皮肤鳞癌进程的机制研究有重要意义并为其防治提供新靶点。

As a kind of electromagnetic radiation, UVB radiation is an important inducement of cutaneous squamous cell carcinoma. The mechanism of non-coding RNA MALAT1 in tumor progression has been a hotspot of research in recent years..Our previous work confirmed that the expression of MALAT1 was increased in the normal keratinocyte line HaCaT after UVB irradiation, and was highly expressed in the cutaneous squamous cell carcinoma tissues and cells. It can promote the malignant biological behaviors of cells and the growth of subcutaneous graft tumors. It can also regulate the expression of Importin7（IPO7）..According to bioinformatics prediction and preliminary experiment results, a scientific hypothesis was proposed that MALAT1 could promote the progression of cutaneous squamous cell carcinoma by regulating the expression of IPO7 to affect the translocation of the transcription factor HIF1αinto the nucleus. Therefore, the main research contents of this project are as follows: ⑴After UVB exposure, MALAT1 regulates the expression of IPO7 to promote the translocate of HIF1α to the nucleus, enhances the transcriptional activity of HIF1α, and induces the occurrence and development of cutaneous squamous cell carcinoma. ⑵The molecular mechanism of the MALAT1-Importin7-HIF1α regulatory axis which affects the progression of cutaneous squamous cell carcinoma..This project provides a new perspective for the study of the regulatory role of lncRNA in tumor progression from the perspective of MALAT1 regulating the expression of importin and affecting transcription factors into the nucleus, which is of great significance for the research on the mechanism of UVB radiation induced cutaneous squamous cell carcinoma progression and provides a new target for its prevention and treatment.