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结直肠癌(CRC)中的调控网络分析表明,[具体内容]影响CRC细胞生物学功能并与miR-6828-5p相互作用。

and Regulatory Network Analysis in Colorectal Cancer (CRC) Reveals That Influences CRC Cell Biological Functions and Interacts with miR-6828-5p.

作者信息

Chen Danqi, Qin Ying, Dai Mengmeng, Li Lulu, Liu Hongpeng, Zhou Yaoyao, Qiu Cheng, Chen Yan, Jiang Yuyang

机构信息

State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Shenzhen, Guangdong, People's Republic of China.

Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital, Shenzhen, Guangdong, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Dec 22;12:13051-13069. doi: 10.2147/CMAR.S277261. eCollection 2020.

Abstract

PURPOSE

We explored specific expression profiles of and genes and studied their biological functions in CRC using bioinformatics tools.

PATIENTS AND METHODS

A total of 68 pairs of cancer and non-cancerous tissues from CRC patients were enrolled in this study. Methods we used in this articles including: qRT-PCR, Western blot analysis, ELISA, GO and KEGG regulatory network analysis, tumor infiltration, luciferase reporter-based protein and etc.

RESULTS

According to The Cancer Genome Atlas (TCGA) data, and expression levels were significantly higher in CRC patient samples than in samples from healthy controls. Moreover, levels were much higher in late-stage CRC than in early-stage disease, warranting evaluation of these genes as CRC prognostic biomarkers. Subsequently, qRT-PCR, Western blot analysis, and ELISA results obtained from analyses of CRC cells, tissues, and patient sera aligned with TCGA results. GO and KEGG regulatory network analysis revealed and associated genes that were functionally related to extracellular matrix (ECM) receptor pathway activation, with transcription factor genes and positively associated with expression and and with expression. Meanwhile, and expression were separately and significantly correlated to tumor infiltration by six immune cell types. Additionally, kinase genes and appeared to be downstream targets of differentially expressed and , respectively. In addition, the expression of mRNA was down-regulated while was down-regulated. Finally, effects on CRC cell proliferation, cycle, apoptosis, invasion, and migration were studied using molecular biological methods, including luciferase reporter-based protein analysis, qRT-PCR, and Western blot results, which revealed that miR-6828-5p may regulate expression.

CONCLUSION

We speculate that the use of and as CRC biomarkers would improve CRC staging, while also providing several novel targets for use in the development of more effective CRC treatments.

摘要

目的

我们使用生物信息学工具探索了[具体基因名称1]和[具体基因名称2]基因的特定表达谱,并研究了它们在结直肠癌中的生物学功能。

患者和方法

本研究纳入了68对来自结直肠癌患者的癌组织和非癌组织。我们在本文中使用的方法包括:qRT-PCR、蛋白质免疫印迹分析、酶联免疫吸附测定、基因本体(GO)和京都基因与基因组百科全书(KEGG)调控网络分析、肿瘤浸润分析、基于荧光素酶报告基因的蛋白质分析等。

结果

根据癌症基因组图谱(TCGA)数据,[具体基因名称1]和[具体基因名称2]在结直肠癌患者样本中的表达水平显著高于健康对照样本。此外,在晚期结直肠癌中的水平远高于早期疾病,这使得评估这些基因作为结直肠癌预后生物标志物具有重要意义。随后,从结直肠癌细胞、组织和患者血清分析中获得的qRT-PCR、蛋白质免疫印迹分析和酶联免疫吸附测定结果与TCGA结果一致。GO和KEGG调控网络分析揭示了[具体基因名称1]和相关基因在功能上与细胞外基质(ECM)受体途径激活相关,转录因子基因[具体转录因子基因名称1]和[具体转录因子基因名称2]分别与[具体基因名称1]表达呈正相关以及与[具体基因名称2]表达呈正相关。同时,[具体基因名称1]和[具体基因名称2]的表达分别与六种免疫细胞类型的肿瘤浸润显著相关。此外,激酶基因[具体激酶基因名称1]和[具体激酶基因名称2]似乎分别是差异表达的[具体基因名称1]和[具体基因名称2]的下游靶点。另外,[具体基因名称3]mRNA的表达下调,而[具体基因名称4]下调。最后,使用分子生物学方法研究了[具体基因名称5]对结直肠癌细胞增殖、周期、凋亡、侵袭和迁移的影响,包括基于荧光素酶报告基因的蛋白质分析、qRT-PCR和蛋白质免疫印迹结果,结果表明miR-6828-5p可能调节[具体基因名称5]的表达。

结论

我们推测使用[具体基因名称1]和[具体基因名称2]作为结直肠癌生物标志物将改善结直肠癌分期,同时也为开发更有效的结直肠癌治疗方法提供几个新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cf/7764722/6510aa624cc8/CMAR-12-13051-g0001.jpg

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