Prognostic value and potential regulatory relationship of miR-200c-5p in colorectal cancer

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Biochemical and Molecular Toxicology Pub Date : 2024-07-17 DOI:10.1002/jbt.23770
Jiying Lu, Zhekang Jin, Xihan Jin, Wenbin Chen
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Abstract

This study aimed to investigate the relationship and potential mechanisms of miR-200c-5p in colorectal cancer (CRC) progression. Differentially expressed miRNAs were screened using the TCGA database. Subsequently, univariate analysis was performed to identify CRC survival-related miRNAs. Survival and receiver operator characteristic curves were generated. The target genes of miR-200c-5p and the relevant signaling pathways or biological processes were predicted by the miRNet database and enrichment analyses. The miR-200c-5p expression was detected using quantitative reverse-transcription polymerase chain reaction, Cell Counting Kit-8, Transwell, and cell apoptosis experiments were performed to determine miR-200c-5p's impact on CRC cell viability, invasiveness, and apoptosis. Finally, we constructed a CRC mouse model with inhibited miR-200c-5p to evaluate its impact on tumors. miR-200c-5p was upregulated in CRC, implying a favorable prognosis. Gene set enrichment analysis revealed that miR-200c-5p may participate in signaling pathways such as the TGF-β signaling pathway, RIG-I-like receptor signaling pathway, renin-angiotensin system, and DNA replication. miR-200c-5p potentially targeted mRNAs, including KCNE4 and CYP1B1, exhibiting a negative correlation with their expression. Furthermore, these mRNAs may participate in biological processes like the regulation of intracellular transport, cAMP-dependent protein kinase regulatory activity, ubiquitin protein ligase binding, MHC class II protein complex binding, and regulation of apoptotic signaling pathway. Lastly, miR-200c-5p overexpression repressed the viability and invasiveness of CRC cells but promoted apoptosis. The tumor size, weight, and volume were significantly increased by inhibiting miR-200c-5p (p < 0.05). miR-200c-5p is upregulated in CRC, serving as a promising biomarker for predicting CRC prognosis.

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miR-200c-5p 在结直肠癌中的预后价值和潜在调控关系。
本研究旨在探讨miR-200c-5p与结直肠癌(CRC)进展的关系和潜在机制。研究利用 TCGA 数据库筛选了差异表达的 miRNA。随后,进行单变量分析以确定与 CRC 生存相关的 miRNA。生成了生存率和接受者操作特征曲线。通过 miRNet 数据库和富集分析预测了 miR-200c-5p 的靶基因和相关信号通路或生物过程。利用反转录聚合酶链反应定量检测 miR-200c-5p 的表达,并进行了细胞计数试剂盒-8、Transwell 和细胞凋亡实验,以确定 miR-200c-5p 对 CRC 细胞活力、侵袭性和凋亡的影响。最后,我们构建了抑制 miR-200c-5p 的 CRC 小鼠模型,以评估其对肿瘤的影响。基因组富集分析显示,miR-200c-5p可能参与了TGF-β信号通路、RIG-I样受体信号通路、肾素-血管紧张素系统和DNA复制等信号通路。此外,这些 mRNA 可能参与细胞内转运调节、cAMP 依赖性蛋白激酶调节活性、泛素蛋白连接酶结合、MHC II 类蛋白复合物结合和凋亡信号通路调节等生物过程。最后,miR-200c-5p 的过表达抑制了 CRC 细胞的活力和侵袭性,但促进了细胞凋亡。抑制 miR-200c-5p 会显著增加肿瘤大小、重量和体积(p
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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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