Malayaperumal Sarubala, Sriramulu Sushmitha, Jothimani Ganesan, Banerjee Antara, Zhang Hong, Mohammed Rafi Shabana Thabassum, Ramachandran Ilangovan, Nr Rajesh Kanna, Sun Xiao-Feng, Pathak Surajit
Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Chennai, India.
Department of Medical Sciences, School of Medicine, Orebro University, Örebro, Sweden.
Ann Med. 2025 Dec;57(1):2478311. doi: 10.1080/07853890.2025.2478311. Epub 2025 Apr 10.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate essential cellular functions, such as cell adhesion, proliferation, migration, invasion, and programmed cell death, and therefore, alterations in miRNAs can contribute to carcinogenesis. Previous studies have shown that miRNA-122 is abundant in the liver and regulates cell proliferation, migration, and apoptosis. However, the expression pattern and mechanism of actions of miR-122 remain primarily unknown in colon cancer.
In this study, we analyzed The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database to assess the clinical significance of astrocyte elevated gene-1 (AEG-1)/metadherin (MTDH) and miR-122 in colon cancer. MiR-122 overexpression studies were performed in HCT116, SW480, and SW620 cell lines. Dual-luciferase assay was carried out to confirm the interaction between AEG-1 and miR-122. -JetPEI-transfection reagent was used for transient transfection of miR-122 in the AOM/DSS-induced colon tumor mouse model.
Our results demonstrate that miR-122 was downregulated in colon cancer cells, and it influences the expressions of apoptotic factors and inflammatory cytokines. MiR-122 overexpression in HCT116, SW480, and SW620 cells showed upregulation of , , and and decreased expression of , which are pro-apoptotic and anti-apoptotic members that maintain a ratio between cellular survival and cell death. transient transfection of miR-122 mimic in AOM/DSS induced colon tumor mouse model showed less inflammation and disease activity. The TCGA-COAD data indicated that AEG-1 expression was higher in patients with low expression of miR-122 and lower AEG-1 expression in patients with higher expression miR-122.
Our findings highlight the key role of miR-122 in the high grade of colonic inflammation, and possibly in colon cancer, and the use of miR-122 mimic might be a therapeutic option.
微小RNA（miRNA）是一类小的非编码RNA，可调节细胞的基本功能，如细胞黏附、增殖、迁移、侵袭和程序性细胞死亡，因此，miRNA的改变可能导致癌症发生。先前的研究表明，miRNA-122在肝脏中含量丰富，并调节细胞增殖、迁移和凋亡。然而，miR-122在结肠癌中的表达模式和作用机制仍不清楚。
在本研究中，我们分析了癌症基因组图谱结肠腺癌（TCGA-COAD）数据库，以评估星形胶质细胞升高基因-1（AEG-1）/黏附素（MTDH）和miR-122在结肠癌中的临床意义。在HCT116、SW480和SW620细胞系中进行了miR-122过表达研究。进行双荧光素酶测定以确认AEG-1与miR-122之间的相互作用。使用-JetPEI转染试剂在AOM/DSS诱导的结肠肿瘤小鼠模型中对miR-122进行瞬时转染。
我们的结果表明，miR-122在结肠癌细胞中表达下调，并且它影响凋亡因子和炎性细胞因子的表达。在HCT116、SW480和SW620细胞中过表达miR-122显示， 、 和 上调， 表达降低，它们分别是促凋亡和抗凋亡成员，维持细胞存活与细胞死亡之间的比例。在AOM/DSS诱导的结肠肿瘤小鼠模型中瞬时转染miR-122模拟物显示炎症和疾病活动较少。TCGA-COAD数据表明，miR-122低表达患者的AEG-1表达较高，而miR-122高表达患者的AEG-1表达较低。
我们的研究结果突出了miR-122在高度结肠炎症以及可能在结肠癌中的关键作用，使用miR-122模拟物可能是一种治疗选择。
