【作者】 周良； 王颖慧； 高琳； 张颖； 高瑞瑞； 郝帅； 刘红霞； 丁振华；

【Author】 ZHOU Liang;WANG Ying-hui;GAO Lin;ZHANG Ying;GAO Rui-rui;HAO Shu-ai;LIU Hong-xia;DING Zhen-hua;Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University;

【机构】 南方医科大学公共卫生学院；

【摘要】 皮肤鳞癌(Cutaneous Squamous Cell Carcinoma,CSCC)恶性程度高、具有较高的淋巴结转移能力,并可沿淋巴组织转移到邻近组织甚至全身,预后较差,5年生存期只有22-56%。紫外辐射是皮肤鳞癌的首要环境危险因子,过量紫外线暴露可导致DNA断裂损伤或内部嘧啶二聚体交联引起基因突变,未完全修复的突变逐渐累积,最终可引发皮肤鳞癌。为寻找皮肤鳞癌中操控肿瘤"生存"的基因,对紫外线照射后的角质形成细胞HaCaT进行转录组学研究,鉴定到了受紫外辐射诱导的非编码RNA miR-365和MALAT1,可促进皮肤鳞癌的发生发展。机制研究发现,miR-365可靶向下调NFIB、BAX和HOXA9等下游靶基因的表达,直接或间接调控细胞周期、细胞凋亡和糖酵解代谢重编程;而长链非编码RNA MALAT1可与c-MYC互作转录调控KTN1表达影响蛋白翻译进程。本系列研究中所鉴别的包括非编码miR-365和MALAT1及其下游信号通路在内的多种靶标,为开发新的治疗手段、有效防治皮肤鳞癌打下良好基础。更多还原

【Abstract】 Cutaneous Squamous Cell Carcinoma(cSCC) is a high degree of malignancy with high lymph node metastasis capacity andpoor prognosis that the 5-year survival period is only 22-56%. Ultraviolet radiation is the primary environmental risk factor for cSCC. Excessive UV exposure can lead to DNA breakage or the formationof pyrimidine dimersleading to gene mutations. Uncompleted mutations gradually accumulate and eventually cause cSCC. To find the gene controlling the "survival" of cSCC, transcriptomic studies were carried out in HaCaT keratinocytes after ultraviolet irradiation and non-coding RNA miR-365 and MALAT1 induced by ultraviolet radiation were identified, which promoted cSCC. Mechanistic studies have found that miR-365 can down-regulate the expression of downstream target genes such as NFIB, BAX and HOXA9, directly or indirectly regulate cell cycle, apoptosis and glycolysis reprogramming. At the same time, long non-coding RNA MALAT1 transcriptionally regulates KTN1 expression by interacting with c-MYC to affect the protein translation process. The therapeutic targets including miR-365, MALAT1 and their downstream signaling pathways provide a good basis to develop new modalities for cSCC prevention and treatment.更多还原