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微小RNA-330-5p/TYMS表达轴在结直肠癌发生机制中的意义

Significance of microRNA-330-5p/TYMS Expression Axis in the Pathogenesis of Colorectal Tumorigenesis.

作者信息

Karimi Leila, Jaberi Milad, Asadi Milad, Zarredar Habib, Zafari Venus, Bornehdeli Soghra, Niknam Saman, Kermani Touraj Asvadi

机构信息

Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Basic Oncology, Health Institute of Ege University, Izmir, Turkey.

出版信息

J Gastrointest Cancer. 2022 Dec;53(4):965-970. doi: 10.1007/s12029-021-00695-x. Epub 2021 Oct 14.

Abstract

BACKGROUND

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. A number of dysregulated microRNAs (miRNAs) have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. microRNA-330 (miR-330-5p) has been reported to inhibit cell proliferation through suppressing thymidylate synthase (TYMS). In the current study, miR-330-5p, TYMS, and their interactions were investigated to evaluate their therapeutic and diagnostic value for CRC treatment.

METHODS

The expression levels of miR-330-5p and TYMS were evaluated in silico using TCGA datasets for CRC. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) utilizing real-time PCR assay. The linkage between clinicopathological parameters and expression levels was also investigated.

RESULTS

TCGA results indicated that miR-330-5p and TYMS were significantly upregulated and downregulated in the CRC, respectively. Real-time PCR results confirmed that the expression of miR-330-5p was significantly upregulated in tumor tissues relative to marginal tissues (P = 0.0005), whereas TYMS expression was significantly downregulated (P = 0.0001). The transcript level of miR-330-5p was associated with tumor stage and lymph node metastases.

CONCLUSION

The microRNA-330 inhibited cell proliferation by suppressing thymidylate synthase (TYMS) in colorectal cancer. Therefore, suggesting that they are valuable factors for further studies of alternative treatment and diagnostic methods.

摘要

背景

结直肠癌(CRC)是全球最常见的癌症类型之一。许多失调的微小RNA(miRNA)与CRC的进展和治疗反应相关,被认为是这种癌症有前景的预后生物标志物。据报道,微小RNA-330(miR-330-5p)通过抑制胸苷酸合成酶(TYMS)来抑制细胞增殖。在本研究中,对miR-330-5p、TYMS及其相互作用进行了研究,以评估它们在CRC治疗中的治疗和诊断价值。

方法

利用CRC的TCGA数据集在计算机上评估miR-330-5p和TYMS的表达水平。利用实时PCR检测对一组内部样本(100对CRC肿瘤标本和相邻非癌样本)进行数据验证。还研究了临床病理参数与表达水平之间的联系。

结果

TCGA结果表明,miR-330-5p和TYMS在CRC中分别显著上调和下调。实时PCR结果证实,相对于边缘组织,肿瘤组织中miR-330-5p的表达显著上调(P = 0.0005),而TYMS表达显著下调(P = 0.0001)。miR-330-5p的转录水平与肿瘤分期和淋巴结转移相关。

结论

微小RNA-330通过抑制结直肠癌中的胸苷酸合成酶(TYMS)来抑制细胞增殖。因此,表明它们是进一步研究替代治疗和诊断方法的有价值因素。

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