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CCNI2 促进结直肠癌的进展。

CCNI2 plays a promoting role in the progression of colorectal cancer.

机构信息

Department of Gastrointestinal Surgery, Sun Yat-sen memorial hospital affiliated Sen Yat-sen University, Guangzhou, China.

Department of Anesthesiology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Cancer Med. 2021 Mar;10(6):1913-1924. doi: 10.1002/cam4.3504. Epub 2021 Feb 23.

Abstract

Colorectal cancer (CRC) is one of the most common malignancies and most of the patients diagnosed with advanced CRC have unsatisfactory treatment effect and poor prognosis. The purpose of this study was to investigate the effect of CCNI2 on the development of CRC. In this sutdy, immunohistochemical staining was used to detect CCNI2 expression levels in clinical samples, meanwhile, the Kaplan-Meier survival analysis was conducted. Celigo cell counting assay was used for screening shCCNI2s. QPCR and WB were performed to verify knockdown efficiency of CCNI2. Cell proliferation, colony formation, cell cycle, apoptosis, and mechanism investigation of CCNI2 knockdown were investigated by MTT assay, colony formation assay, fluorescence-activated cell sorting, and human apoptosis antibody array, respectively. Otherwise, the mouse model of CCNI2 knockdown was also constructed. The results of immunohistochemical staining and qPCR indicated that CCNI2 had a high expression level in the CRC tissues and cell lines. Kaplan-Meier survival analysis manifested that the high expression of CCNI2 suggested poor prognosis. The expression of CCNI2 was significantly reduced by CCNI2-siRNAs, and the downregulated expression level of CCNI2 inhibited CRC cell proliferation and colony formation, arrested cell cycle in G2 phase, as well as promoted cell apoptosis. The various indexes of solid tumor in mice models indicated that CCNI2 knockdown could suppress the growth of CRC tumor. Based on the comprehensive analysis of the above results, CCNI2 was contributed to the progression of CRC and could serve as a prognostic marker for CRC.

摘要

结直肠癌(CRC)是最常见的恶性肿瘤之一,大多数被诊断为晚期 CRC 的患者治疗效果不佳,预后较差。本研究旨在探讨 CCNI2 对 CRC 发展的影响。在本研究中,采用免疫组织化学染色检测临床样本中 CCNI2 的表达水平,同时进行 Kaplan-Meier 生存分析。Celigo 细胞计数检测用于筛选 shCCNI2s。QPCR 和 WB 用于验证 CCNI2 的敲低效率。通过 MTT 检测、集落形成检测、荧光激活细胞分选和人凋亡抗体阵列分别研究 CCNI2 敲低对细胞增殖、集落形成、细胞周期、细胞凋亡和机制的影响。此外,还构建了 CCNI2 敲低的小鼠模型。免疫组织化学染色和 qPCR 的结果表明,CCNI2 在 CRC 组织和细胞系中表达水平较高。Kaplan-Meier 生存分析表明 CCNI2 高表达提示预后不良。CCNI2-siRNAs 显著降低 CCNI2 的表达,下调 CCNI2 的表达水平抑制 CRC 细胞增殖和集落形成,使细胞周期停滞在 G2 期,并促进细胞凋亡。小鼠模型中实体瘤的各项指标表明 CCNI2 敲低可抑制 CRC 肿瘤的生长。基于对上述结果的综合分析,CCNI2 有助于 CRC 的进展,可以作为 CRC 的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/399e/7957193/698dc36e1e96/CAM4-10-1913-g003.jpg

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