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血清 miR-658 通过激活 PAX3-MET 通路诱导胃癌转移:一项基于人群的研究。

Serum miR-658 induces metastasis of gastric cancer by activating PAX3-MET pathway: A population-based study.

机构信息

Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

Department of Breast and Thyroid Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Cancer Biomark. 2018;22(1):111-118. doi: 10.3233/CBM-171045.

DOI:10.3233/CBM-171045
PMID:29630524
Abstract

BACKGROUND AND OBJECTIVE

MiR-658, paired box gene 3 (PAX3) and met proto-oncogene (MET) are overexpressed in gastric cancer while PAX3 and MET can be regulated by miRNA. Serum miR-658 may be associated with metastasis of gastric cancer (MGC) by affecting PAX3-MET pathway.

METHODS

Ninety-eight gastric carcinoma patients with distant MGC (DM group) and ninety-six gastric carcinoma patients with no MGC (NM group) were recruited. Serum miR-658 was validated between DM and NM groups by using quantitative reverse transcription PCR (qRT-PCR). PAX3 and MET levels were measured by Western Blot. The molecular mechanism for the function of serum miR-658 was further validated in gastric cell lines.

RESULTS

The results demonstrate that serum level of miR-658 is significantly lower in the NM group than in the DM group (P< 0.001). Meanwhile, the levels of PAX3 and MET are lower in the NM group than in the DM group too (P< 0.01). Both overexpression and silence of miR-658 significantly up-regulate or down-regulate the levels of PAX3 and MET in gastric cell lines (P< 0.05).

CONCLUSIONS

The present findings demonstrate that elevated circulating miR-658 is associated with MGC by activating PAX3-MET pathway.

摘要

背景与目的

微小 RNA-658(miR-658)、配对盒基因 3(PAX3)和间质上皮转化因子(MET)在胃癌中过度表达,而 PAX3 和 MET 可以被 miRNA 调控。血清 miR-658 可能通过影响 PAX3-MET 通路与胃癌(MGC)的转移有关。

方法

招募了 98 例远处转移性胃癌(DM 组)和 96 例无远处转移性胃癌(NM 组)患者。采用实时定量逆转录 PCR(qRT-PCR)验证 DM 组和 NM 组之间血清 miR-658 的差异。采用 Western blot 检测 PAX3 和 MET 水平。进一步在胃细胞系中验证血清 miR-658 功能的分子机制。

结果

结果表明,NM 组血清 miR-658 水平明显低于 DM 组(P<0.001)。同时,NM 组 PAX3 和 MET 的水平也低于 DM 组(P<0.01)。miR-658 的过表达和沉默均显著上调或下调胃细胞系中 PAX3 和 MET 的水平(P<0.05)。

结论

本研究结果表明,升高的循环 miR-658 通过激活 PAX3-MET 通路与 MGC 相关。

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