脂肪细胞外泌体circTHBS1通过调节胆固醇转运促进乳腺癌转移的机制研究

Adipocyte exosomes promote breast cancer metastasis. CircTHBS1 (circ for short) is a novel circRNA that was screened by chip technology and was highly expressed in adipocyte exosomes. Previous studies have found that adipocyte exosome circ promoted breast cancer metastasis. Bioinformatics and pre-experiments suggested that circ acted as the sponge for miR-33a, while miR-33a inhibits ABCA1 expression. Besides, silencing circ could decrease ABCA1 mRNA and protein expressions. Also clinical data suggested that ABCA1 could promote breast cancer metastasis. Therefore we raise this hypothesis: Adipocyte exosomes mediate circ to promote breast cancer metastasis through inhibiting miR-33a and enhancing ABCA1-related cholesterol transport. Our study intends to apply the rescue strategy, immunofluorescence and other techniques to confirm that adipocyte exosome circ might reverse the inhibition of ABCA1 induced by miR-33a in the molecular, cellular, animal and clinical aspects. At present, there is rarely report about the relationship between adipocyte exosome circ and breast cancer metastasis. This study will reveal the mechanism of adipocyte exosome circ promoting breast cancer metastasis from a new perspective, thus providing new ideas for the treatments of breast cancer.

脂肪细胞外泌体能够促进乳腺癌转移。CircTHBS1（简称circ）是通过circRNA芯片技术筛选出来、在脂肪细胞外泌体显著高表达的新型circRNA。前期研究发现：脂肪细胞外泌体circ促进乳腺癌的转移，生物信息学和预实验提示circ吸附miR-33a，而miR-33a抑制ABCA1的表达，沉默circ能降低ABCA1 mRNA和蛋白的表达。临床数据提示ABCA1能够促进乳腺癌转移。据此提出假说：脂肪细胞介导外泌体circ抑制miR-33a，增强ABCA1相关的胆固醇转运，促进乳腺癌转移。本研究拟从分子、细胞、动物、临床等层面，利用拯救策略、免疫荧光等技术证实脂肪细胞外泌体circ逆转miR-33a对ABCA1的抑制，最终促进乳腺癌转移的机制。目前尚无脂肪细胞外泌体circ与乳腺癌转移的报道，本研究将从脂肪细胞外泌体circ的新视点揭示其促进乳腺癌转移的机制，为乳腺癌的治疗提供新思路。

脂肪细胞及其外泌体能够促进乳腺癌转移。CircCNIH4（简称circ）在与脂肪细胞共培养的乳腺癌细胞中被显著抑制，并通过生物信息学和预实验提示circ吸附miR-135b，miR-135b结合FOXO1并调控上皮间质转化过程。本研究从分子、细胞、动物、临床等层面，利用拯救策略、免疫荧光等技术证实脂肪细胞促进乳腺癌的转移，脂肪细胞外泌体抑制circ吸附miR-135b，并调控FOXO1介导的上皮间质转化过程，最终促进乳腺癌转移。目前鲜有脂肪细胞外泌体参与circ表达及乳腺癌转移的报道，本研究从脂肪细胞外泌体介导的circ这一全新视点揭示脂肪细胞促进乳腺癌转移的机制，为肥胖相关乳腺癌的治疗提供新思路。同时我们发现脂肪因子vaspin通过抑制miR-33a/ABHD2而促进乳腺癌的转移，为肥胖相关乳腺癌患者提供新型生物标志物，有助于提高乳腺癌患者的预后。