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细胞因子信号抑制因子3在结肠癌侵袭与增殖调控机制中的作用

[Role of cytokine signal suppressor 3 in the regulatory mechanism of colon cancer invasion and proliferation].

作者信息

Hong Zhu, Zhang Xipeng

机构信息

Department of Anal and Intestinal Surgery, Tianjin Union Medical Center (Nankai University Affiliated Hospital), Tianjin 300121, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2019 Jan 30;39(1):43-48. doi: 10.12122/j.issn.1673-4254.2019.01.07.

DOI:10.12122/j.issn.1673-4254.2019.01.07
PMID:30692065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6765584/
Abstract

OBJECTIVE

To investigate the expression of cytokine signal suppressor 3 (SOCS3) in colon cancer tissue and the mechanism by which SOCS3 regulates the proliferation and invasion of colon cancer.

METHODS

We collected the specimens of tumor tissues and paired adjacent tissues from 80 patients with colon cancer undergoing radical resection in our hospital between July, 2014 and May, 2017, and the expression of SOCS3 in the tissue samples was analyzed using Western blotting. We also transfected colon cancer cell line SW480 with a SOCS3-overexpressing plasmid or a small interference RNA (siRNA) for SOCS3 knockdown, and the changes in the cell proliferation and invasion capacity were evaluated using CCK-8 assay and Transwell assay, respectively. The effect of demethylation and IL-6 treatment on SOCS3 expression and the proliferation and invasion of SW480 cells were observed.

RESULTS

Colon cancer tissues showed a lowered expression of SOCS3 compared with the adjacent tissues. Over-expression of SOCS3 significantly inhibited while SOCS3 knockdown obviously promoted the proliferation and invasion of SW480 cells . Demethylation treatment up-regulated SOCS3 expression and inhibited the proliferation and invasion capacity of SW480 cells; IL-6 treatment of the cells caused the reverse changes.

CONCLUSIONS

SOCS3 participates in the development and progression of colon cancer and serves as a potential target for colon cancer treatment. In patients with colon cancer, the low expression of SOCS3 possibly as a result of methylation may promote the proliferation and invasion of the cancer cells.

摘要

目的

探讨细胞因子信号抑制因子3(SOCS3)在结肠癌组织中的表达情况以及SOCS3调控结肠癌增殖和侵袭的机制。

方法

收集2014年7月至2017年5月在我院接受根治性切除术的80例结肠癌患者的肿瘤组织标本及配对的癌旁组织标本,采用蛋白质免疫印迹法分析组织样本中SOCS3的表达。我们还用SOCS3过表达质粒或用于敲低SOCS3的小干扰RNA(siRNA)转染结肠癌细胞系SW480,分别采用CCK-8法和Transwell法评估细胞增殖和侵袭能力的变化。观察去甲基化和IL-6处理对SW480细胞SOCS3表达及增殖和侵袭的影响。

结果

与癌旁组织相比,结肠癌组织中SOCS3表达降低。SOCS3过表达显著抑制而敲低SOCS3明显促进SW480细胞的增殖和侵袭。去甲基化处理上调SOCS3表达并抑制SW'480细胞的增殖和侵袭能力;用IL-6处理细胞则导致相反的变化。

结论

SOCS3参与结肠癌的发生发展,可作为结肠癌治疗的潜在靶点。在结肠癌患者中,SOCS3低表达可能由于甲基化导致,可促进癌细胞的增殖和侵袭。

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本文引用的文献

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Correlation of SOCS-1 gene with onset and prognosis of breast cancer.SOCS-1基因与乳腺癌发病及预后的相关性
Oncol Lett. 2018 Jul;16(1):383-387. doi: 10.3892/ol.2018.8675. Epub 2018 May 9.
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MiR-155 regulates lymphoma cell proliferation and apoptosis through targeting SOCS3/JAK-STAT3 signaling pathway.miR-155 通过靶向 SOCS3/JAK-STAT3 信号通路调节淋巴瘤细胞增殖和凋亡。
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Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion via effects on cancer-associated fibroblasts.糖皮质激素通过对肿瘤相关成纤维细胞的作用间接降低结肠癌的增殖和侵袭。
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SOCS3 participates in cholinergic pathway regulation of synovitis in rheumatoid arthritis.信号转导及转录激活因子3(SOCS3)参与类风湿关节炎滑膜炎的胆碱能通路调节。
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Upregulation of GNL3 expression promotes colon cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway.GNL3表达上调通过Wnt/β-连环蛋白信号通路促进结肠癌细胞的增殖、迁移、侵袭及上皮-间质转化。
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Gene. 2017 Sep 5;627:114-122. doi: 10.1016/j.gene.2017.06.013. Epub 2017 Jun 8.
7
Muscle-specific deletion of SOCS3 does not reduce the anabolic response to leucine in a mouse model of acute inflammation.在急性炎症小鼠模型中,肌肉特异性缺失SOCS3不会降低对亮氨酸的合成代谢反应。
Cytokine. 2017 Aug;96:274-278. doi: 10.1016/j.cyto.2017.05.016. Epub 2017 May 26.
8
Relationship between HER2 and JAK/STAT-SOCS3 signaling pathway and clinicopathological features and prognosis of ovarian cancer.HER2与JAK/STAT-SOCS3信号通路的关系及与卵巢癌临床病理特征和预后的相关性
Cancer Biol Ther. 2017 May 4;18(5):314-322. doi: 10.1080/15384047.2017.1310343. Epub 2017 Apr 27.
9
Resistin causes G1 arrest in colon cancer cells through upregulation of SOCS3.抵抗素通过上调细胞因子信号转导抑制因子3(SOCS3)导致结肠癌细胞的G1期阻滞。
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10
Mer receptor tyrosine kinase negatively regulates lipoteichoic acid-induced inflammatory response via PI3K/Akt and SOCS3.Mer受体酪氨酸激酶通过PI3K/Akt和SOCS3负向调节脂磷壁酸诱导的炎症反应。
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