Cysteine-Rich Intestinal Protein 1 Silencing Inhibits Migration and Invasion in Human Colorectal Cancer
Cysteine-Rich Intestinal Protein 1 Silencing Inhibits Migration and Invasion in Human Colorectal Cancer
复制标题
富含半胱氨酸的肠蛋白 1 沉默抑制人结直肠癌的迁移和侵袭
DOI：
10.1159/000485357
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Cui, Jing
中科院分区：
文献类型：
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作者：
He, Guoyang;Zou, Liyuan;Cui, Jing
背景/目的：富含半胱氨酸的肠蛋白1 （CRIP1）是LIM/双锌指蛋白家族的一员，在几种肿瘤类型中异常表达。然而，关于CRIP1在癌症中的作用的数据很少。在本研究中，我们旨在研究CRIP1在结直肠癌中的表达谱和功能。方法：对56对结肠癌组织标本进行免疫组化（IHC）检测CRIP1蛋白表达水平。Western blotting检测四种结肠癌细胞系中CRIP1蛋白的表达。使用短干扰rna （sirna）抑制内源性CRIP1的表达。细胞增殖试验用于确定CRIP1沉默是否影响细胞增殖。流式细胞术检测细胞凋亡。通过transwell和伤口愈合实验检测沉默CRIP1对细胞迁移和侵袭的影响。结果：免疫组化分析显示，肿瘤组织样本中CRIP1蛋白水平明显高于配对的非肿瘤组织样本，转移组织样本中CRIP1蛋白水平高于非转移组织样本。此外，高转移结肠癌细胞系中CRIP1蛋白水平高于低转移结肠癌细胞系。此外，CRIP1沉默对SW620和HT29细胞的增殖和凋亡没有影响。CRIP1沉默可明显抑制SW620和HT29细胞的迁移和侵袭。结论：本研究提供了新的证据，表明CRIP1的异常表达可能与结直肠癌的转移程度有关，而CRIP1的沉默可以有效抑制结直肠癌发展过程中的迁移和侵袭。这些发现可能有助于开发结肠癌预后和转移的生物标志物，从而有助于治疗这种常见类型的癌症。
Background/Aims: Cysteine-rich intestinal protein 1 (CRIP1), a member of the LIM/double zinc finger protein family, is abnormally expressed in several tumour types. However, few data are available on the role of CRIP1 in cancer. In the present study, we aimed to investigate the expression profile and functions of CRIP1 in colorectal cancer. Methods: To examine the protein expression level of CRIP1, immunohistochemistry (IHC) was performed on 56 pairs of colon cancer tissue samples. Western blotting was performed to investigate CRIP1 protein expression in four colon cancer cell lines. The endogenous expression of CRIP1 was suppressed using short interfering RNAs (siRNAs). Cell proliferation assays were used to determine whether CRIP1 silencing affected cell proliferation. Flow cytometry analysis was used to detect cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion was detected using the transwell and wound-healing assays. Results: IHC analysis showed that protein level of CRIP1 was significantly higher in tumour tissue samples than in paired non-tumour tissue samples and that the CRIP1 level was higher in metastatic tissue samples than in non-metastatic tissue samples. In addition, protein levels of CRIP1 were higher in highly metastatic colon cancer cell lines than in colon cancer cell lines with low metastasis. Further, CRIP1 silencing had no effect on cell proliferation or apoptosis in SW620 and HT29 cells. CRIP1 silencing suppressed cell migration and invasion obviously in SW620 and HT29 cells. Conclusion: The present study provides new evidence that abnormal expression of CRIP1 might be related to the degree of metastasis in colorectal cancer and that CRIP1 silencing could effectively inhibit migration and invasion during colorectal cancer development. These findings might aid the development of a biomarker for colon cancer prognosis and metastasis, and thus help to treat this common type of cancer.