Martínez-Gutierrez Antonio, Carbajal-Lopez Berenice, Bui Triet M, Mendoza-Rodriguez Monica, Campos-Parra Alma D, Calderillo-Ruiz Germán, Cantú-De Leon David, Madrigal-Santillán Eduardo-Osiris, Sumagin Ronen, Pérez-Plasencia Carlos, Pérez-Yépez Eloy-Andrés
Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, Mexico.
Programa de Doctorado en Investigación en Medicina, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico.
Biochem Biophys Rep. 2022 Mar 18;30:101252. doi: 10.1016/j.bbrep.2022.101252. eCollection 2022 Jul.
Colon cancer (CC) is the third most common neoplasm and the fourth cause of cancer-related death worldwide in both sexes. It has been established that inflammation plays a critical role in tumorigenesis and progression of CC. Immune, stromal and tumor cells supply the tumor microenvironment with pro-inflammatory cytokines such as interleukin 1β, TNFα, IL-6 and IL-11, to hyperactivate signaling pathways linked to cancerous processes. Recent findings suggest a putative role of microRNAs (miRNAs) in the progression and management of the inflammatory response in intestinal diseases. Moreover, miRNAs are able to regulate expression of molecular mediators that are linking inflammation and cancer. In this work a miRNA panel differentially expressed between healthy, inflammatory bowel disease (IBD) and CC tissue was established. Identified miRNAs regulate signaling pathways related to inflammation and cancer progression. An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. Finally, differential miRNA expression was validated using an inflammation-associated CC model induced by Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) to compare miRNA expression in normal and inflamed tissue versus CC tissues. Based on these findings we propose the identified inflammatory miRNA panel as a potent diagnostic tool for CC determination.
结肠癌（CC）是全球男女中第三大常见肿瘤，也是癌症相关死亡的第四大原因。炎症在CC的肿瘤发生和进展中起着关键作用，这一点已经得到证实。免疫细胞、基质细胞和肿瘤细胞为肿瘤微环境提供促炎细胞因子，如白细胞介素1β、肿瘤坏死因子α、白细胞介素6和白细胞介素11，以过度激活与癌变过程相关的信号通路。最近的研究结果表明，微小RNA（miRNA）在肠道疾病炎症反应的进展和管理中可能发挥作用。此外，miRNA能够调节连接炎症和癌症的分子介质的表达。在这项研究中，建立了一个在健康、炎症性肠病（IBD）和CC组织之间差异表达的miRNA谱。鉴定出的miRNA调节与炎症和癌症进展相关的信号通路。发现由11种miRNA组成的炎症相关miRNA谱在CC中过度表达，但在炎症或正常组织中未过度表达（miR-21-5p、miR-304-5p、miR-577、miR-335-5p、miR-21-3p、miR-27b-5p、miR-335-3p、miR-215-5p、miR-30b-5p、miR-192-5p、miR-306-5p）。使用Kaplan-Meier检验证明了排名靠前的miRNA，即miR-3065-5p和miR-30b-5p表达与CC患者总生存期的相关性。最后，使用由氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）诱导的炎症相关CC模型验证差异miRNA表达，以比较正常和炎症组织与CC组织中的miRNA表达。基于这些发现，我们提出鉴定出的炎症性miRNA谱作为CC诊断的有效工具。
