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沉默UBE2D1可抑制胃癌细胞迁移，减少SMAD4的泛素化。

Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4.

作者信息

Xie Honghu, He Yu, Wu Yugang, Lu Qicheng

机构信息

Department of Gastrointestinal Surgery, The First People's Hospital of Changzhou, 185 Juqian Street, Changzhou, 213000, Jiangsu, China.

出版信息

Infect Agent Cancer. 2021 Nov 7;16(1):63. doi: 10.1186/s13027-021-00402-2.

DOI:10.1186/s13027-021-00402-2
PMID:34743754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8574036/
Abstract

BACKGROUND

Gastric cancer (GC) is the second leading cause of cancer-related deaths. Because it is hard to diagnose at early stage, the overall 5 years survival rate is lower than 25%. High migration is the main hallmark of malignant cells at advanced stage of GC. Thus, it is urgent to find biomarkers for early diagnosis and more effective therapy of GC.

METHODS

In this study, lentivirus-mediated silencing and overexpression lentiviruses targeting the ubiquitin-conjugating enzyme E2 D1 (UBE2D1), transwell, wound healing, and pulmonary metastasis mouse model were applied to analyze the function of UBE2D1 in vitro and in vivo. Real-time PCR and immunohistochemistry were used to elucidate the level of UBE2D1 in GC samples.

RESULTS

Silencing of UBE2D1 inhibited cell migration and the levels of epithelial-mesenchymal transition makers (MMP2 and MMP9) in AGS and MKN45 cells. Silencing of UBE2D1 inhibited cell metastasis in mouse model. On the contrary, UBE2D1 overexpression increased cell migration and the levels of MMP2 and MMP9 in MGC-803 cells. Further, silencing of UBE2D1 decreased the ubiquitination level of mothers against decapentaplegic homolog 4 (SMAD4), and the increase of cell migration induced by UBE2D1 overexpression could be reversed by SMAD4.

CONCLUSION

Silencing of UBE2D1 inhibited cell migration through transforming growth factor β (TGF-β)/SMAD4 signaling pathway in GC.

摘要

背景

胃癌（GC）是癌症相关死亡的第二大主要原因。由于其在早期难以诊断，总体5年生存率低于25%。高迁移率是GC晚期恶性细胞的主要标志。因此，迫切需要寻找用于GC早期诊断和更有效治疗的生物标志物。

方法

在本研究中，应用慢病毒介导的针对泛素结合酶E2 D1（UBE2D1）的沉默和过表达慢病毒、Transwell实验、伤口愈合实验以及肺转移小鼠模型来分析UBE2D1在体外和体内的功能。采用实时PCR和免疫组织化学方法来阐明GC样本中UBE2D1的水平。

结果

沉默UBE2D1可抑制AGS和MKN45细胞的迁移以及上皮-间质转化标志物（MMP2和MMP9）的水平。沉默UBE2D1可抑制小鼠模型中的细胞转移。相反，UBE2D1过表达增加了MGC-803细胞的迁移以及MMP2和MMP9的水平。此外，沉默UBE2D1降低了母亲对果蝇节腹基因同源物4（SMAD4）的泛素化水平，并且UBE2D1过表达诱导的细胞迁移增加可被SMAD4逆转。

结论

沉默UBE2D1通过转化生长因子β（TGF-β）/SMAD4信号通路抑制GC细胞的迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/066a2e28fbe1/13027_2021_402_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/e65fe868688d/13027_2021_402_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/f049ee7d1ac4/13027_2021_402_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/a767b1af1335/13027_2021_402_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/4223c9a54fd7/13027_2021_402_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/15fcb9992689/13027_2021_402_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/066a2e28fbe1/13027_2021_402_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/e65fe868688d/13027_2021_402_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/f049ee7d1ac4/13027_2021_402_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/a767b1af1335/13027_2021_402_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/4223c9a54fd7/13027_2021_402_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/15fcb9992689/13027_2021_402_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc12/8574036/066a2e28fbe1/13027_2021_402_Fig6_HTML.jpg

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