染料木黄酮通过TTTY18/ miR-95/ SGK1环路干预结直肠癌细胞增殖凋亡的作用及机制研究

Colorectal cancer (CRC) is one of the common malignant tumors, and its occurrence and development are affected by many factors. Our previous studies also showed that genistein can inhibit SGK1, inactivate PIK/Akt signaling pathway and inhibit CRC cell proliferation and induce apoptosis by regulating miR-95 and SGK1. Recent studies found that GeneChip® Human Transcriptome Array 2.0 long-chain non-coding RNA microarray was used to observe the changes of LncRNAs in CRC cells treated with Genistein (50μM). Results showed the study confirmed that TTTY18 interacts with miR-95, and then targets SGK1 protein, with a ring-like interaction among the three. Based on this, we hypothesized that genistein exerts an anti-tumor effect by modulating TTTY18/miR-95/SGK1 loop-mediated phosphorylation of MAPK/PI3K signaling pathways, affecting downstream apoptotic pathways, and inhibiting proliferation of colorectal cancer cells. In this experiment, the clear effects and mechanism of genistein on colorectal cancer cells were observed by in vitro and in vivo experiments using cell biology, molecular biology, dual luciferase reporter assays, flow cytometry, and nude mouse models and for the development of genistein, a natural anti-cancer drug to provide solid experimental evidence.

结直肠癌（CRC）是常见的恶性肿瘤之一，而它的发生发展受多种因素的影响，研究表明非编码RNA在其中扮演重要角色。我们前期的研究表明植物雌激素—染料木黄酮可以通过下调miR-95，抑制SGK1、失活PI3K/Akt信号通路，产生抑制CRC细胞增殖、诱导凋亡的作用。课题组最近通过LncRNA基因芯片、生物信息学观察到染料木黄酮显著下调LncRNA TTTY18，而TTTY18、miR-95、SGK1三者之间呈环状相互影响。本项目将通过体内、外实验，利用细胞生物学、分子生物学、双荧光素酶报告基因实验、流式细胞术、裸鼠模型等技术方法观察染料木黄酮通过干预TTTY18、miR-95、SGK1环路，失活下游MAPK/PI3K信号通路，抑制结直肠癌细胞增殖、诱导其凋亡，为染料木黄酮及同类药物对结直肠癌的开发应用提供切实可靠的实验证据。

结直肠癌（CRC）是常见的恶性肿瘤之一，而它的发生发展受多种因素的影响，研究表明非编码RNA在其中扮演重要角色。我们前期的研究表明植物雌激素—染料木黄酮可以通过下调miR-95，抑制SGK1、失活PI3K/Akt信号通路，产生抑制CRC细胞增殖、诱导凋亡的作用。课题组最近通过LncRNA基因芯片、生物信息学观察到染料木黄酮显著下调LncRNA TTTY18，而TTTY18、miR-95、SGK1三者之间呈环状相互影响。本项目通过体内、外实验，利用细胞生物学、分子生物学、双荧光素酶报告基因实验、流式细胞术、裸鼠荷瘤模型等技术方法验证染料木黄酮通过干预TTTY18/miR-95/SGK1环路，介导MAPK/PI3K/Akt信号通路的蛋白磷酸化情况及凋亡蛋白水平，从而抑制结直肠癌细胞增殖、转移，诱导其凋亡，为染料木黄酮及同类药物对结直肠癌的抗肿瘤作用提供切实可靠的实验证据。