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血清 miR-133b 和 miR-206 下调与转移性结直肠癌患者进展的临床结局相关,可作为监测的生物标志物。

Downregulation of Serum miR-133b and miR-206 Associate with Clinical Outcomes of Progression as Monitoring Biomarkers for Metastasis Colorectal Cancer Patients.

机构信息

College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand.

Biomedical Science Research Unit, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand.

出版信息

Microrna. 2024;13(1):56-62. doi: 10.2174/0122115366266024240101075745.

Abstract

BACKGROUND

Colorectal cancer (CRC) is the third most common cancer in the world. Noncoding RNAs or microRNAs (miRNAs; miRs) biomarkers can play a role in cancer carcinogenesis and progression. Specific and mutation are associated with CRC development playing a role in controlling the cellular process as epigenetic events. Circulating serum miRs can serve for early diagnosis, monitoring, and prognosis of CRC as biomarkers but it is still unclear, clinically.

OBJECTIVE

To determine potential biomarkers of circulating serum miR-133b and miR-206 in CRC patients Methods: Bioinformatic prediction of microRNA was screened followed by TargetScanHuman7.2, miRTar2GO, miRDB, MiRanda, and DIANA-microT-CDS. Forty-four CRC serum (19 locally advanced, 23 distant advanced CRC) and 12 normal serum samples were subsequently extracted for RNA isolation, cDNA synthesis, and miR validation. The candidate circulating serum miR-133b and miR-206 were validated resulting in a relative expression via quantitative RT-PCR. Relative expression was normalized to the spike-internal control and compared to normal samples as 1 using the -2ΔΔCt method in principle.

RESULTS

Our results represented 9 miRs of miR-206, miR-155-5p, miR-143-3p, miR-193a-3p, miR-30a- 5p, miR-30d-5p, miR-30e-5p, miR-543, miR-877-5p relate to KRAS-specific miRs, whereas, 9 miRs of miR-133b, miR-302a-3p, miR-302b-3p, miR-302d-3p, miR-302e, miR-520a-3p, miR-520b, miR-520c- 3p and miR-7-5p relevance to EGFR-specific miRs by using the bioinformatic prediction tools. Our results showed a decreased expression level of circulating serum miR-133b as well as miR-206 associating with CRC patients (local and advanced metastasis) when compared to normal (P < 0.05), significantly.

CONCLUSION

The circulating serum miR-133b and miR-206 can serve as significant biomarkers for monitoring the clinical outcome of progression with metastatic CRC patients. Increased drug-responsive CRC patients associated with crucial molecular intervention should be further explored, clinically.

摘要

背景

结直肠癌(CRC)是世界上第三大常见癌症。非编码 RNA 或 microRNAs(miRNAs;miRs)生物标志物可在癌症发生和进展中发挥作用。特定的突变与 CRC 的发展有关,在作为表观遗传事件的细胞过程中发挥作用。循环血清 miR 可作为生物标志物用于 CRC 的早期诊断、监测和预后,但在临床上仍不清楚。

目的

确定 CRC 患者循环血清 miR-133b 和 miR-206 的潜在生物标志物。

方法

对 microRNA 进行生物信息学预测筛选,然后使用 TargetScanHuman7.2、miRTar2GO、miRDB、miRanda 和 DIANA-microT-CDS。随后提取 44 例 CRC 血清(19 例局部晚期,23 例远处转移 CRC)和 12 例正常血清样本进行 RNA 分离、cDNA 合成和 miR 验证。通过实时定量 RT-PCR 验证候选循环血清 miR-133b 和 miR-206 的相对表达。通过 -2ΔΔCt 方法将相对表达归一化为内参 Spike,并与正常样本进行比较,作为 1。

结果

我们的结果代表了 miR-206 的 9 个 miR、miR-155-5p、miR-143-3p、miR-193a-3p、miR-30a-5p、miR-30d-5p、miR-30e-5p、miR-543 和 miR-877-5p 与 KRAS 特异性 miR 有关,而 miR-133b 的 9 个 miR、miR-302a-3p、miR-302b-3p、miR-302d-3p、miR-302e、miR-520a-3p、miR-520b、miR-520c-3p 和 miR-7-5p 与 EGFR 特异性 miR 有关通过生物信息学预测工具。我们的结果表明,与正常对照组相比,CRC 患者(局部和晚期转移)循环血清 miR-133b 和 miR-206 的表达水平降低(P<0.05),具有显著统计学意义。

结论

循环血清 miR-133b 和 miR-206 可作为监测转移性 CRC 患者临床进展的有意义的生物标志物。应进一步探索与增加药物反应性 CRC 患者相关的关键分子干预,临床上。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc8/11275315/8f56c6302263/MIRNA-13-56_F1.jpg

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