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微小 RNA-204-3p 通过下调 MGAT1 抑制胰腺癌的转移。

MicroRNA-204-3p inhibits metastasis of pancreatic cancer via downregulating MGAT1.

机构信息

Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China.

出版信息

J BUON. 2021 Sep-Oct;26(5):2149-2156.

Abstract

PURPOSE

We aimed to clarify the relationship between microRNA-204-3p level and clinical indicators in pancreatic cancer patients, and to provide theoretical references for target therapy.

METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect relative levels of microRNA-204-3p and MGAT1 in 60 paired pancreatic cancer tissues and adjacent normal ones. The relationship between microRNA-204-3p level and clinical indicators in pancreatic cancer patients was analyzed. MicroRNA-204-3p overexpression model was established in AsPC-1 and CFPAC-1 cells. Transwell and wound healing assay were carried out to illustrate the influence of microRNA-204-3p on the migratory potential in pancreatic cancer. Lastly luciferase assay and rescue experiments were performed to demonstrate the potential mechanism between microRNA-204-3p and MGAT1.

RESULTS

MicroRNA-204-3p was lowly expressed in pancreatic cancer tissues. Low level of microRNA-204-3p predicted high rates of lymphatic metastasis and distant metastasis, as well as poor prognosis in pancreatic cancer patients. Overexpression of microRNA-204-3p inhibited pancreatic cancer cells to migrate in vitro. MicroRNA-204-3p could be targeted by MGAT1 through specific binding sites in the 3'UTR. A negative correlation between MGAT1 and microRNA-204-3p was identified in pancreatic cancer tissues. The interaction between MGAT1 and microRNA-204-3p was responsible for inhibiting metastasis of pancreatic cancer.

CONCLUSIONS

MicroRNA-204-3p is closely linked to lymphatic metastasis, distant metastasis and prognosis in pancreatic cancer patients. It inhibits the migratory ability in pancreatic cancer cells via negatively regulating MGAT1 level.

摘要

目的

我们旨在阐明 microRNA-204-3p 水平与胰腺癌患者临床指标之间的关系,并为靶向治疗提供理论参考。

方法

采用实时定量聚合酶链反应(qRT-PCR)检测 60 对胰腺癌组织及其相邻正常组织中 microRNA-204-3p 和 MGAT1 的相对水平。分析胰腺癌患者 microRNA-204-3p 水平与临床指标的关系。在 AsPC-1 和 CFPAC-1 细胞中建立 microRNA-204-3p 过表达模型。Transwell 和划痕愈合实验用于说明 microRNA-204-3p 对胰腺癌迁移能力的影响。最后通过荧光素酶报告基因实验和挽救实验验证 microRNA-204-3p 与 MGAT1 之间的潜在机制。

结果

microRNA-204-3p 在胰腺癌组织中低表达。microRNA-204-3p 水平低预示着胰腺癌患者的淋巴转移和远处转移率高,预后差。microRNA-204-3p 的过表达抑制了胰腺癌细胞的体外迁移。microRNA-204-3p 可以通过 3'UTR 中的特异性结合位点靶向 MGAT1。在胰腺癌组织中鉴定到 MGAT1 和 microRNA-204-3p 之间存在负相关。MGAT1 和 microRNA-204-3p 之间的相互作用负责抑制胰腺癌的转移。

结论

microRNA-204-3p 与胰腺癌患者的淋巴转移、远处转移和预后密切相关。它通过负调控 MGAT1 水平抑制胰腺癌细胞的迁移能力。

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