健脾复方下调MALAT1抑制大肠癌侵袭转移的机制研究

Invasion and metastasis is one of the most important factors that affect the 5-year survival rate of colorectal cancer patients, and MALAT1 can promote tumor cells invasion and migration through exosomes. Our previous study found that MALAT1 knock down HCT116 cells can inhibit the invasion and metastasis of colorectal cancer, and regulate the expression of Wnt3a/5a. Further study found that exosomes from colorectal cancer cells expressed Wnt3a/5a; Jianpi Compound Recipe can down-regulated the expression of MALAT1 in a dose dependent manner, and inhibited the activation of Wnt/β-catenin pathway. Therefore, we speculate that MALAT1 may inhibit the invasion and metastasis of colorectal cancer through Exo-Wnt protein mediated β-catenin. We will prove it by WB, qRT-PCR, Transwell, NTA, and exosomes co incubation experiments. This study will clarify the mechanism of MALAT1 regulating colorectal cancer cell invasion and metastasis through Exo-Wnt3a/5a；And also reveal the molecular mechanism of Jianpi compound inhibits the invasion and metastasis of colorectal carcinoma. It will provide key clues for studying the mechanism of therapeutic effect of Jianpi compound.

侵袭转移是影响大肠癌术后5年生存率的重要原因之一，MALAT1可通过外泌体促进肿瘤细胞的侵袭和迁移。我们前期研究发现，HCT116细胞中沉默MALAT1能抑制大肠癌的侵袭和转移，调控Wnt3a/5a的表达，进一步研究发现大肠癌肿瘤细胞外泌体中含有Wnt3a/5a；健脾复方以剂量依赖型方式下调MALAT1的表达，抑制Wnt/β-catenin通路的活化。因此我们推测健脾复方下调MALAT1可能通过Exo-Wnt蛋白介导β-catenin抑制大肠癌侵袭转移。本研究拟构建过表达和沉默MALAT1的大肠癌细胞株，采用WB、qRT-PCR、Transwell、NTA、外泌体共孵育等实验，明确MALAT1调控Exo-Wnt3a/5a影响大肠癌细胞侵袭转移的机制；通过体内外干预实验，进一步揭示健脾复方抑制大肠癌侵袭转移的分子机制，为健脾复方治疗作用的机理研究提供关键线索。

侵袭转移是影响大肠癌术后5年生存率的重要原因之一，MALAT1可通过外泌体促进肿瘤细胞的侵袭和迁移。我们前期研究发现，HCT116细胞中沉默MALAT1能抑制大肠癌的侵袭和转移，调控Wnt3a/5a的表达，进一步研究发现大肠癌肿瘤细胞外泌体中含有Wnt3a/5a；健脾复方以剂量依赖型方式下调MALAT1的表达，抑制Wnt/β-catenin通路的活化。因此我们推测健脾复方下调MALAT1可能通过Exo-Wnt蛋白介导β-catenin抑制大肠癌侵袭转移。本研究拟构建过表达和沉默MALAT1的大肠癌细胞株，采用WB、qRT-PCR、Transwell、NTA、外泌体共孵育等实验，明确MALAT1调控Exo-Wnt3a/5a影响大肠癌细胞侵袭转移的机制；通过体内外干预实验，进一步揭示健脾复方抑制大肠癌侵袭转移的分子机制，为健脾复方治疗作用的机理研究提供关键线索。