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CXCL14在结直肠癌中的表达及作用

Expression and effect of CXCL14 in colorectal carcinoma.

作者信息

Lin Kezhi, Zou Ruanmin, Lin Feng, Zheng Shuang, Shen Xian, Xue Xiangyang

机构信息

Experimental Teaching Center, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.

出版信息

Mol Med Rep. 2014 Sep;10(3):1561-8. doi: 10.3892/mmr.2014.2343. Epub 2014 Jun 17.

Abstract

Chemokines are important in the proliferation and metastasis of tumors. CXCL14 is a member of the CXCL chemokine family and exhibits various expression patterns in different types of tumor, even those tumors that occur in the same type of tissue. The expression of CXCL14 and its clinical significance in colorectal carcinoma are unclear. In the present study, the expression levels of CXCL14 in colorectal carcinoma and adjacent normal tissues were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Kaplan‑Meier survival curves and the Cox regression model were applied to evaluate the clinical significance of the expression levels of CXCL14 in colorectal carcinoma compared with those in normal tissues. To investigate the effects at a cellular level, a replication‑defective lentivirus overexpressing CXCL14 was constructed and transfected into HT29 colorectal carcinoma cells. The effect of CXCL14 on the proliferation of colorectal carcinoma cells and the change in cell cycle distributions were investigated using a cell counting kit‑8 assay and flow cytometry, respectively. Results of the current study indicated that the expression levels of CXCL14 mRNA and protein in colorectal carcinoma were markedly reduced compared with levels in normal tissues (P<0.05). The clinical correlation analysis suggested that downregulation of CXCL14 expression in tumors was associated with lymph metastasis, tumor location, and clinicopathological stage (P<0.05). Kaplan‑Meier survival analysis revealed that downregulation of CXCL14 expression was correlated with a poor prognosis (P<0.01). Overexpression of CXCL14 by lentiviral transfection produced an inhibitory effect on cell proliferation by arresting the cell cycle in the G1 stage. The data of the current study suggest that CXCL14 may be involved in the development and progression of colorectal carcinoma, and may act directly as a potential cancer suppressor gene. The level of CXCL14 expression may be a valuable adjuvant parameter in predicting the prognosis of colorectal carcinoma and may be a potential therapeutic target.

摘要

趋化因子在肿瘤的增殖和转移中起重要作用。CXCL14是CXCL趋化因子家族的成员,在不同类型的肿瘤中呈现出多种表达模式,即使是发生在同一类型组织中的肿瘤也是如此。CXCL14在结直肠癌中的表达及其临床意义尚不清楚。在本研究中,采用逆转录定量聚合酶链反应和免疫组织化学方法检测CXCL14在结直肠癌组织及癌旁正常组织中的表达水平。应用Kaplan-Meier生存曲线和Cox回归模型评估结直肠癌组织中CXCL14表达水平与正常组织相比的临床意义。为了在细胞水平上研究其作用,构建了过表达CXCL14的复制缺陷型慢病毒并转染至HT29结直肠癌细胞中。分别使用细胞计数试剂盒-8检测法和流式细胞术研究CXCL14对结直肠癌细胞增殖的影响以及细胞周期分布的变化。本研究结果表明,与正常组织相比,结直肠癌组织中CXCL14 mRNA和蛋白的表达水平明显降低(P<0.05)。临床相关性分析表明,肿瘤中CXCL14表达下调与淋巴结转移、肿瘤位置及临床病理分期相关(P<0.05)。Kaplan-Meier生存分析显示,CXCL14表达下调与预后不良相关(P<0.01)。慢病毒转染过表达CXCL14通过使细胞周期停滞在G1期对细胞增殖产生抑制作用。本研究数据表明,CXCL14可能参与了结直肠癌的发生和发展,并且可能直接作为一种潜在的抑癌基因发挥作用。CXCL14的表达水平可能是预测结直肠癌预后的一个有价值的辅助参数,并且可能是一个潜在的治疗靶点。

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