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小核核糖核蛋白多肽N通过E2F8转录调控加速结直肠癌的恶性进展并导致不良预后。

Small Nuclear Ribonucleoprotein Polypeptide N Accelerates Malignant Progression and Poor Prognosis in Colorectal Cancer Transcriptionally Regulated by E2F8.

作者信息

Ji Meiling, Ren Li, Lv Yang, Lao Xinyuan, Feng Qingyang, Tang Wentao, Zhuang Aobo, Liu Tianyu, Zheng Peng, Xu Jianmin

机构信息

Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China.

出版信息

Front Oncol. 2020 Nov 2;10:561287. doi: 10.3389/fonc.2020.561287. eCollection 2020.

Abstract

Colorectal cancer is a major cause of death worldwide, and the identification of new diagnostic and prognostic biomarkers is crucial to develop new strategies to avoid colorectal cancer-related deaths. Small nuclear ribonucleoprotein polypeptide N (SNRPN) is an imprinted gene that plays an important role in various neurodevelopmental disabilities. In this study, SNRPN was highly expressed in colorectal cancer tissues and involved in the progression of this disease. Immunohistochemistry analysis of 1,310 colorectal cancer tissue samples showed that SNRPN highly expressed in cancer tissues than in adjacent tissues and was mainly localized in the nucleus. Clinical pathological factor analysis demonstrated that higher expression of SNRPN was significantly associated with larger tumor size, location of the tumor on the left-sided colon, neural invasion, and distant metastasis. Univariate and multivariate analyses showed that SNRPN expression was an independent risk factor for survival, with high expression levels indicating worse overall survival. Both and experiments confirmed that high expression of SNRPN was associated with tumor proliferation, cell cycle, and metastasis. Knocking down SNRPN blocked the cell cycle at the G2/M phase transition and promoted tumor cell apoptosis, inhibiting the progression of colorectal cancer. To explore the up-steam of SNRPN, we found by luciferase reporter assay and chromosomal immunoprecipitation assay that E2F8 was a transcriptional regulator up-steam of SNRPN in colorectal cancer. Systematic studies of SNRPN will help us discover new regulatory molecules and provide a theoretical basis for finding new molecular targets for this disease.

摘要

结直肠癌是全球主要的死亡原因之一,识别新的诊断和预后生物标志物对于制定避免结直肠癌相关死亡的新策略至关重要。小核核糖核蛋白多肽N(SNRPN)是一种印记基因,在各种神经发育障碍中起重要作用。在本研究中,SNRPN在结直肠癌组织中高表达,并参与了该疾病的进展。对1310份结直肠癌组织样本进行免疫组织化学分析显示,SNRPN在癌组织中的表达高于相邻组织,且主要定位于细胞核。临床病理因素分析表明,SNRPN的高表达与肿瘤较大的尺寸、肿瘤位于左半结肠、神经侵犯和远处转移显著相关。单因素和多因素分析表明,SNRPN表达是生存的独立危险因素,高表达水平表明总体生存率较差。体外和体内实验均证实,SNRPN的高表达与肿瘤增殖、细胞周期和转移相关。敲低SNRPN可使细胞周期阻滞在G2/M期转换,并促进肿瘤细胞凋亡,从而抑制结直肠癌的进展。为了探索SNRPN的上游机制,我们通过荧光素酶报告基因检测和染色体免疫沉淀检测发现,E2F8是结直肠癌中SNRPN的转录调节上游因子。对SNRPN进行系统研究将有助于我们发现新的调节分子,并为寻找该疾病的新分子靶点提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d83/7669248/02363d309608/fonc-10-561287-g0001.jpg

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