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计算机分析和实验验证表明 miR-1183 与结直肠癌细胞周期进展基因 1 的表达呈负相关。

In silico analysis and experimental validation shows negative correlation between miR-1183 and cell cycle progression gene 1 expression in colorectal cancer.

机构信息

Department of Biosciences, Cancer Genetics and Epigenetics Lab, COMSATS University Islamabad, Islamabad, Pakistan.

Maroof International Hospital, Islamabad, Pakistan.

出版信息

PLoS One. 2023 Aug 4;18(8):e0289082. doi: 10.1371/journal.pone.0289082. eCollection 2023.

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by binding to the 3' untranslated regions (UTR) of target genes. Aberrant expression of miRNAs can lead to disease, including cancer. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Among several factors, differential expression of miRNA can have serious consequences on disease progression. This study was designed to computationally identify and experimentally verify strong miRNA candidates that could influence CRC progression. In silico analysis of publicly available gene expression microarray datasets revealed significant upregulation of miR-1183 in CRC. Comparison of mRNA microarray expression data with predicted miR-1183 targets led to the identification of cell cycle progression gene 1 (CCPG1) as strong, negatively correlated miR-1183 target. Expression analysis by means of quantitative PCR validated the inverse correlation between miR-1183 and CCPG1 in colorectal cancer tissues. CCPG1 indirectly modulates the cell cycle by interacting with the PH/DH domain of Dbs (Rho-specific guanine nucleotide exchange factor). Interestingly, the computational analysis also showed that miR-1183 is upregulated in liver and gastric cancer. This finding is notable as the liver and stomach are the primary metastatic sites for colorectal cancer and hepatocellular carcinoma respectively. This novel finding highlights the broader implications of miR-1183 dysregulation beyond primary CRC, potentially serving as a valuable prognostic marker and a therapeutic target for both primary and metastatic CRC.

摘要

微小 RNA(miRNA)是一种小的非编码 RNA,通过与靶基因的 3'非翻译区(UTR)结合,在后转录水平上调节基因表达。miRNA 的异常表达可导致疾病,包括癌症。结直肠癌(CRC)是全球癌症相关死亡的主要原因之一。在多种因素中,miRNA 的差异表达可能对疾病进展产生严重后果。本研究旨在通过计算方法鉴定和实验验证可能影响 CRC 进展的强 miRNA 候选物。对公开的基因表达微阵列数据集进行的计算机分析显示,CRC 中 miR-1183 的表达显著上调。与预测的 miR-1183 靶基因的 mRNA 微阵列表达数据进行比较,导致细胞周期进展基因 1(CCPG1)作为强烈的、负相关的 miR-1183 靶基因被鉴定出来。通过定量 PCR 进行的表达分析验证了 miR-1183 和 CCPG1 在结直肠癌细胞组织中的负相关关系。CCPG1 通过与 Dbs(Rho 特异性鸟苷酸交换因子)的 PH/DH 结构域相互作用间接调节细胞周期。有趣的是,计算分析还显示 miR-1183 在肝癌和胃癌中上调。这一发现值得注意,因为肝脏和胃是结直肠癌和肝细胞癌的主要转移部位。这一新发现强调了 miR-1183 失调的更广泛意义超出了原发性 CRC,可能成为原发性和转移性 CRC 的有价值的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3226/10403070/1f07dca50609/pone.0289082.g001.jpg

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