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结蛋白-2 在结直肠癌中通过上皮-间充质转化和 MAPK 通路发挥致癌作用。

Syndecan-2 in colorectal cancer plays oncogenic role via epithelial-mesenchymal transition and MAPK pathway.

机构信息

Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226021, Jiangsu, PR China.

Department of Hematology, Affiliated Hospital of Nantong University, Nantong 226021, Jiangsu, PR China.

出版信息

Biomed Pharmacother. 2020 Jan;121:109630. doi: 10.1016/j.biopha.2019.109630. Epub 2019 Nov 7.

DOI:10.1016/j.biopha.2019.109630
PMID:31707342
Abstract

PURPOSE

In this study, we aimed to elucidate the biological roles of Syndecan-2 (SDC2) in colorectal cancer (CRC), thereby further understanding its clinical role.

METHODS

The expression of SDC2 was assessed by qRT-PCR and Western blot analysis. To understand the potential biological role of SDC2, we also explored the correlation between its expression level and clinicopathologic parameters. By using MTT, plate colony formation assay, Transwell invasion assays, and flow cytometry in vitro, the biological impact of SDC2 on CRC cell proliferation, migration, invasion, and apoptosis. In addition, the related signaling pathways were investigated.

RESULTS

SDC2 expression was significantly upregulated in CRC tissues. The expression of SDC2 was highly associated with four parameters, i.e., stage (P < 0.01), vascular invasion (P = 0.0045), lymph node metastasis (P=0.0018), and distant metastasis (P = 0.0019). Knockdown of SDC2 significantly reduced proliferation, migration, and invasion of HCT116 and SW480 cells, and induced cell apoptosis. Moreover, SDC2 promoted epithelial-mesenchymal transition (EMT) in CRC cells, whereas the ratio of p-MEK/MEK and p-ERK/ERK markedly reduced after depleting SDC2.

CONCLUSION

During CRC development, overexpression of SDC2 plays a carcinogenic role in CRC. Therapeutic solutions targeting SDC2 may provide potential insights into CRC prevention and treatment.

摘要

目的

本研究旨在阐明硫酸乙酰肝素蛋白聚糖-2(SDC2)在结直肠癌(CRC)中的生物学作用,从而进一步了解其临床作用。

方法

通过 qRT-PCR 和 Western blot 分析评估 SDC2 的表达。为了了解 SDC2 的潜在生物学作用,我们还探讨了其表达水平与临床病理参数之间的相关性。通过 MTT、平板克隆形成实验、Transwell 侵袭实验和流式细胞术体外研究 SDC2 对 CRC 细胞增殖、迁移、侵袭和凋亡的生物学影响。此外,还研究了相关信号通路。

结果

SDC2 在 CRC 组织中表达明显上调。SDC2 的表达与四个参数高度相关,即分期(P<0.01)、血管侵犯(P=0.0045)、淋巴结转移(P=0.0018)和远处转移(P=0.0019)。SDC2 敲低显著降低 HCT116 和 SW480 细胞的增殖、迁移和侵袭能力,并诱导细胞凋亡。此外,SDC2 促进 CRC 细胞的上皮间质转化(EMT),而在耗尽 SDC2 后,p-MEK/MEK 和 p-ERK/ERK 的比值明显降低。

结论

在 CRC 发展过程中,SDC2 的过表达在 CRC 中发挥致癌作用。针对 SDC2 的治疗方法可能为 CRC 的预防和治疗提供潜在的见解。

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