Department of Pathology, School of Medicine, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea.
Digestive Disease Research Institute, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea.
Genes Genomics. 2023 Oct;45(10):1295-1304. doi: 10.1007/s13258-023-01432-3. Epub 2023 Jul 31.
Human microRNA 452 (MIR452) has been linked to both colorectal cancer (CRC) tissues and dextran sulfate sodium (DSS)-induced colitis.
We analyzed the correlation between MIR452 and its putative target gene in human CRC cells and in mouse colitis tissues.
Luciferase reporter assay confirmed that Src homologous and collagen adaptor protein 1 (SHC1) is a direct target of MIR452. Furthermore, the expression of proteins or mRNA was assessed by immunohistochemical analysis, Western blot, or quantitative RT-PCR (qRT-PCR).
We found that MIR452 has a potential binding site at 3'-UTR of SHC1. Likewise, MIR452 or siSHC1 transfection dramatically reduced the level of cellular SHC1 in CRC cells. The expression of SHC1 was frequently downregulated in both human CRC tissues and mouse colitis tissues. In CRC cells, we demonstrated that MIR452 regulated the expression of genes involved in the SHC1-mediated KRAS-MAPK signal transduction pathways.
These findings suggest a potential defense mechanism in which MIR452 regulation of the adaptor protein SHC1 maintains cellular homeostasis during carcinogenesis or chronic inflammation. Therefore, MIR452 may have therapeutic value for human early-stage CRC and colitis.
人类 microRNA 452（MIR452）与结直肠癌（CRC）组织和葡聚糖硫酸钠（DSS）诱导的结肠炎有关。
我们分析了 MIR452 与其在人 CRC 细胞和小鼠结肠炎组织中的假定靶基因之间的相关性。
荧光素酶报告基因检测证实 Src 同源和胶原接头蛋白 1（SHC1）是 MIR452 的直接靶基因。此外，通过免疫组织化学分析、Western blot 或定量 RT-PCR（qRT-PCR）评估蛋白质或 mRNA 的表达。
我们发现 MIR452 在 SHC1 的 3'-UTR 上具有潜在的结合位点。同样，MIR452 或 siSHC1 转染可显著降低 CRC 细胞中细胞 SHC1 的水平。SHC1 的表达在人 CRC 组织和小鼠结肠炎组织中均频繁下调。在 CRC 细胞中，我们证明 MIR452 调节了 SHC1 介导的 KRAS-MAPK 信号转导途径中涉及的基因的表达。
这些发现表明，MIR452 调节接头蛋白 SHC1 的表达可能是一种潜在的防御机制，在致癌作用或慢性炎症过程中维持细胞内稳态。因此，MIR452 可能对人类早期 CRC 和结肠炎具有治疗价值。
