CSRP1 Promotes Colon Adenocarcinoma Growth and Serves as an Independent Risk Biomarker for Worse Prognosis.

IF 1.4 4区 生物学 Q4 GENETICS & HEREDITY
Senlong Yu, Haifeng Zhao, Hongjie Meng, Shengguang Shi, Shenghui Cao, Tianhua Bian, Canping Ruan
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Abstract

Background: Cysteine and Glycine Rich Protein 1 (CSRP1) belongs to the cysteine-rich protein family, which contains a unique double-zinc finger motif and is important for development and cellular differentiation. Abnormal expression of CSRP1 was reported within several malignancies such as prostate cancer and acute myeloid leukemia. Here, we explored function of CSRP1 within colon adenocarcinoma (COAD) for the first time.

Methods: The mRNA levels of CSRP1 in COADs were obtained from TCGA datasets. CSRP1 protein expressions in COADs were tested via immunohistochemistry staining. Patients' prognosis was evaluated using both univariate analysis and multivariate analysis. Two human COAD originated cancer cell lines, Caco-2, and HT-29, were used for cellular experiments including shRNA knockdown, proliferation assay, and migration assay. In vivo model was established using nude mice xenografts to further validate the role of CSRP1 in COAD progression.

Results: The mRNA levels of CSRP1 are elevated in COAD specimens from patients with more advanced tumor stages and higher Carcinoembryonic Antigen (CEA) levels. In addition, higher CSRP1 mRNA level indicates worse COAD prognosis. Consistently, higher CSRP1 protein expression is correlated with worse overall survival according to both univariate and multivariate analysis, indicating that CSRP1 is a new COAD prognostic factor. Furthermore, COAD cells transfected with CSRP1-shRNAs exhibit attenuated proliferation and migration capacities. Finally, growth of xenografts originated from CSRP1-knockdown cells is inhibited comparing to the control ones.

Conclusions: Expression of CSRP1 is positively correlated with COAD progression, which can promote tumor growth and migration. Higher CSRP1 can is a novel independent prognostic factor of COAD.

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CSRP1促进结肠腺癌生长并作为预后不良的独立风险生物标志物。
背景:富含半胱氨酸和甘氨酸的蛋白1 (CSRP1)属于富含半胱氨酸的蛋白家族,含有独特的双锌指基序,对发育和细胞分化具有重要意义。在前列腺癌和急性髓性白血病等多种恶性肿瘤中,都报道了CSRP1的异常表达。本研究首次探讨了CSRP1在结肠腺癌(COAD)中的功能。方法:从TCGA数据中获取COADs中CSRP1的mRNA水平。免疫组织化学染色检测COADs中CSRP1蛋白的表达。采用单因素分析和多因素分析评估患者预后。两个人类COAD来源的癌细胞系Caco-2和HT-29用于细胞实验,包括shRNA敲除、增殖实验和迁移实验。采用裸鼠异种移植建立体内模型,进一步验证CSRP1在COAD进展中的作用。结果:在晚期肿瘤患者的COAD标本中,CSRP1 mRNA水平升高,癌胚抗原(CEA)水平升高。此外,较高的CSRP1 mRNA水平表明COAD预后较差。单因素和多因素分析一致表明,高CSRP1蛋白表达与较差的总生存相关,表明CSRP1是一个新的COAD预后因素。此外,转染了CSRP1-shRNAs的COAD细胞表现出增殖和迁移能力减弱。最后,与对照细胞相比,源自csrp1敲低细胞的异种移植物的生长受到抑制。结论:CSRP1表达与COAD进展呈正相关,可促进肿瘤生长和迁移。较高的CSRP1可能是COAD的一个新的独立预后因素。
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来源期刊
Genetics research
Genetics research 生物-遗传学
自引率
6.70%
发文量
74
审稿时长
>12 weeks
期刊介绍: Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.
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