Leptin介导lncRNA SOCAR/NONO通路在肿瘤-脂肪微环境中调控糖脂代谢重编程促进卵巢癌进展的机制研究

腹腔转移是卵巢癌患者预后不良的主要原因之一，富含脂肪的大网膜是最常见的转移部位。前期工作发现lncRNA SOCAR促进卵巢癌细胞糖脂代谢重编程和侵袭迁移，上调NONO蛋白的水平；敲低NONO可以抑制卵巢癌细胞代谢重编程和侵袭；脂肪细胞共培养上调卵巢癌细胞SOCAR的水平，促进侵袭；leptin抗体可部分逆转脂肪细胞共培养对卵巢癌细胞的上述影响。提出假说:大网膜脂肪细胞分泌leptin促进卵巢癌细胞SOCAR的转录；SOCAR通过NONO激活卵巢癌细胞糖脂代谢重编程、促进卵巢癌的转移进展。课题组拟深入研究leptin介导SOCAR/NONO通路调控卵巢癌细胞糖脂代谢重编程促进肿瘤进展的分子机制，筛选靶向NONO的小分子抑制剂并明确其抑制卵巢癌腹腔转移的作用，希望进一步明确肿瘤-脂肪微环境促进卵巢癌转移的调控机制，为卵巢癌治疗提供新靶点。

Peritoneal metastasis is one of the leading causes of the poor prognosis of ovarian carcinoma patients. The omentum rich in adipocytes is the most common site of metastasis. We found that lncRNA SOCAR not only promoted reprogramming of glucose and lipid metabolism and invasion and migration of ovarian carcinoma cells but also upregulated NONO protein level; NONO knockdown reduced reprogramming of glucose and lipid metabolism and invasion of ovarian carcinoma cells; adipocytes co-culture upregulated SOCAR level and promoted invasion of ovarian carcinoma cells; leptin antibody partially reversed the influence of adipocytes co-culture on ovarian carcinoma cells. So we hypothesize that leptin secreted by adipocytes of omentum promotes SOCAR transcription of ovarian carcinoma cells; SOCAR activates the reprogramming of glucose and lipid metabolism through binding to NONO protein, which promotes metastasis and progression of ovarian carcinoma. In this project, we will investigate the regulation mechanism of SOCAR/NONO pathway induced by leptin on reprogramming of glucose and lipid metabolism and progression of ovarian carcinoma. We will also screen small molecule inhibitors targeting NONO and explore its inhibition effect on metastasis of ovarian carcinoma. The objective of the study is to illuminate the regulation mechanism of adipose-tumor microenvironment promoting metastasis of ovarian carcinoma and provide new targets for ovarian carcinoma therapy.