The mechanisms of colorectal cancer cell mesenchymal-epithelial transition induced by hepatocyte exosome-derived miR-203a-3p.

The mechanisms of colorectal cancer cell mesenchymal-epithelial transition induced by hepatocyte exosome-derived miR-203a-3p.
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肝细胞外泌体来源的miR-203a-3p诱导结直肠癌细胞间质-上皮转化的机制

DOI:
10.1186/s12885-021-08419-x
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发表时间:
2021-06-19
期刊:
影响因子:
3.8
通讯作者:
Chu Z
Chu Z
中科院分区:
医学2区
文献类型:
--
作者:
Xu H;Lan Q;Huang Y;Zhang Y;Zeng Y;Su P;Chu Z;Lai W;Chu Z

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肝转移是结直肠癌(CRC)患者最常见的死亡原因。再生肝磷酸酶-3通过上皮向间质转化诱导CRC转移,这促进CRC细胞肝转移。间充质-上皮转化(MET),上皮-间充质转化的对立面,已被提出作为转移性肿瘤形成的机制。然而,MET的分子机制仍不清楚。使用免疫组织化学、蛋白质印迹、侵袭测定、实时定量PCR、染色质免疫沉淀、荧光素酶报告基因测定、人miRNA阵列和异种移植小鼠模型,我们确定了肝细胞外泌体衍生的miR-203 a-3 p在CRC MET中的作用。在我们的研究中,我们发现来源于肝细胞外泌体的miR-203 a-3 p增加结直肠癌细胞E-cadherin表达,抑制Src表达,并降低活性。以这种方式,miR-203 a-3 p诱导CRC细胞的侵袭率降低。来源于肝细胞外泌体的MiR-203 a-3 p在CRC细胞在肝脏定植中发挥着重要作用。
Liver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear. Using Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET. In our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells. MiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.
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