Identification of stool miR-135b-5p as a non-invasive diaognostic biomarker in later tumor stage of colorectal cancer,Life Sciences

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Identification of stool miR-135b-5p as a non-invasive diaognostic biomarker in later tumor stage of colorectal cancer
Life Sciences ( IF 5.2 ) Pub Date : 2020-09-12 , DOI: 10.1016/j.lfs.2020.118417
Li Li ₁ , Aili Wang ₂ , Min Cai ₁ , Minsi Tong ₁ , Fengtao Chen ₁ , Ling Huang ₁

Affiliation

Colorectal cancer (CRC) is one of the most common cancers. However, the effective and non-invasive diagnostic biomarkers for the detection of CRC metastasis remain unsatisfied. Here, we aimed to evaluate the diagnostic performance of stool miR-135b-5p (a potential biomarker) for metastasis of CRC patients. Serum and stool specimens from 77 patients with CRC and 29 normal controls were collected for miRNA purification. Real-time quantitative PCR was used for the relative quantification of miR-135b-5p expression. Receiver operating and characteristic (ROC) curve analysis was used to estimate the diagnostic performance of stool/serum miR-135b-5p for CRC metastasis. Dual-luciferase reporter assay was conducted to determine miR-135b-5p's target gene. Besides, a trans-well matrigel assay was performed to evaluate the invasion ability of HT-29 cell lines. Stool miR-135b-5p expression was dramatically up-regulated in CRC patients, and it effectively distinguished the CRC patients from normal controls with 74.1% of specificity and 96.5% of sensitivity. Moreover, stool miR-135b-5p exhibited a better diagnostic performance in distinguishing the different TNM stages of CRC patients than serum miR-135b-5p. In the molecular mechanism, our observations indicated that miR-135-5p directly targets the mRNA of ZNRF3, and then activates the Wnt pathway. Over-expression of ZNRF3 in HT-29 cells obviously reversed miR-135b-5p's effects on cell invasion and migration, indicating miR-135b-5p achieves its biological functions in a ZNRF3 dependent manner. MiR-135b-5p may be a promising non-invasive biomarker for the diagnosis of CRC patients with TNM stage-III/IV and a potential candidate to develop an intervention strategy for colorectal cancer.

中文翻译：

粪便 miR-135b-5p 鉴定为结直肠癌晚期非侵入性诊断生物标志物

结直肠癌（CRC）是最常见的癌症之一。然而，用于检测CRC转移的有效且非侵入性的诊断生物标志物仍然不令人满意。在这里，我们的目的是评估粪便 miR-135b-5p（一种潜在的生物标志物）对 CRC 患者转移的诊断性能。收集 77 例 CRC 患者和 29 例正常对照的血清和粪便标本进行 miRNA 纯化。使用实时定量PCR对miR-135b-5p表达进行相对定量。使用受试者工作和特征（ROC）曲线分析来评估粪便/血清 miR-135b-5p 对 CRC 转移的诊断性能。进行双荧光素酶报告基因测定以确定miR-135b-5p的靶基因。此外，还进行了跨孔基质胶实验来评估HT-29细胞系的侵袭能力。 CRC 患者粪便中 miR-135b-5p 表达显着上调，可有效区分 CRC 患者与正常对照，特异性为 74.1%，敏感性为 96.5%。此外，粪便miR-135b-5p在区分CRC患者不同TNM分期方面表现出比血清miR-135b-5p更好的诊断性能。在分子机制上，我们的观察表明miR-135-5p直接靶向ZNRF3的mRNA，然后激活Wnt通路。 ZNRF3在HT-29细胞中的过表达明显逆转了miR-135b-5p对细胞侵袭和迁移的影响，表明miR-135b-5p以ZNRF3依赖性方式实现其生物学功能。 MiR-135b-5p 可能是一种有前途的非侵入性生物标志物，用于诊断 TNM III/IV 期 CRC 患者，也是制定结直肠癌干预策略的潜在候选者。

更新日期：2020-09-12

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