Wang Pengfei, Li Gang, Sun Xianglin, Zhang Jie, Shi Leijian, Zhou Xiaoyu, Wang Guohua, Chen Weichang
Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
Department of Gastroenterology, Affiliated Qidong Hospital of Nantong University, Qidong, 226200, Jiangsu, China.
Eur J Med Res. 2025 May 2;30(1):352. doi: 10.1186/s40001-025-02625-0.
Colorectal cancer (CRC), a complex and multifactorial disease, has been associated with elevated expression of microRNA miR-182-5p, although its precise regulatory role in CRC progression remains unclear. This study aims to identify potential therapeutic targets to improve clinical outcomes and to decipher the intricate role of miR-182-5p in the pathobiology of CRC.
We conducted comprehensive bioinformatics analyses using GEO databases to investigate differences in miRNA expression between CRC and normal tissues, with a particular focus on miR-182-5p. Its expression levels in CRC cells and tumor tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of neurocalcin delta (NCALD) and proteins related to Wnt/β-catenin signalling was evaluated by qRT-PCR and Western blotting. Pathological changes in tumor-bearing mice as well as the proliferation, invasion, and migration of CRC cells, were assessed. Tumor cell proliferation and apoptosis were examined using Ki-67 immunohistochemistry and TUNEL staining, respectively. A dual luciferase reporter assay explored the regulatory interaction between miR-182-5p and NCALD.
Our findings reveal significantly elevated miR-182-5p levels in CRC tissues and cell lines, positively correlated with tumor invasion depth, differentiation degree, clinical stage, and lymph node metastasis. miR-182-5p appears to accelerate CRC progression in both cell lines and mouse models by downregulating NCALD, thereby enhancing Wnt/β-catenin signalling. This study identifies miR-182-5p as a pivotal enhancer of CRC progression, modulating Wnt/β-catenin signalling via NCALD regulation.
The findings position the miR-182-5p/NCALD axis as promising targets for CRC therapy, offering new avenues for treatment strategies.
Retrospectively registered.
结直肠癌（CRC）是一种复杂的多因素疾病，与微小RNA miR-182-5p的表达升高有关，尽管其在CRC进展中的精确调控作用仍不清楚。本研究旨在确定潜在的治疗靶点以改善临床结果，并阐明miR-182-5p在CRC病理生物学中的复杂作用。
我们使用GEO数据库进行了全面的生物信息学分析，以研究CRC组织与正常组织之间miRNA表达的差异，特别关注miR-182-5p。通过定量实时PCR（qRT-PCR）对其在CRC细胞和肿瘤组织中的表达水平进行定量。通过qRT-PCR和蛋白质印迹法评估神经钙蛋白δ（NCALD）以及与Wnt/β-连环蛋白信号传导相关的蛋白质的表达。评估荷瘤小鼠的病理变化以及CRC细胞的增殖、侵袭和迁移。分别使用Ki-67免疫组织化学和TUNEL染色检测肿瘤细胞增殖和凋亡。双荧光素酶报告基因检测探讨了miR-182-5p与NCALD之间的调控相互作用。
我们的研究结果显示，CRC组织和细胞系中miR-182-5p水平显著升高，与肿瘤浸润深度、分化程度、临床分期和淋巴结转移呈正相关。miR-182-5p似乎通过下调NCALD来加速CRC在细胞系和小鼠模型中的进展，从而增强Wnt/β-连环蛋白信号传导。本研究确定miR-182-5p是CRC进展的关键增强因子，通过调控NCALD来调节Wnt/β-连环蛋白信号传导。
这些发现将miR-182-5p/NCALD轴定位为CRC治疗的有前景的靶点，为治疗策略提供了新途径。
回顾性注册。
