PDF(Pubmed)
Abstract：
BACKGROUND: Colorectal Cancer (CRC) is the third most common cancer type and the second leading cause of cancer-related deaths worldwide. However, the existing treatment, as well as prognosis strategies for CRC patients, need to be improved in order to increase the chance of survival. Targeted therapies of CRC, as opposed to ordinary therapies, target key biological features and pathways of cancerous cells hence minimizing the subsequent damage to normal cells. MicroRNAs have been reported to play a crucial role in inhibiting and/or suppressing major pathways in various cancer types by targeting transcripts of key genes in such pathways.
METHODS: The purpose of this study was to analyze in silico the differentially expressed genes from five microarray datasets of patients with CRC. Furthermore, miRNAs were investigated to inhibit cancer cell proliferation and metastasis by targeting a key gene-frizzled receptor 3 (FZD3) in the Wnt signaling pathway.
RESULTS: The Wnt pathway receptor FZD3 is upregulated in CRC along with other pathway genes, which play a critical role in tumorigenesis. In contrast, miR-98-5p inhibits the activity of FZD3 by binding directly to the 3\'UTR of its mRNA, therefore exerting a suppressor effect on colorectal tumors.
CONCLUSIONS: The study reveals miR-98-5p as a novel target of FZD3 and an inhibitor of the Wnt signaling pathway hence being a potential candidate for developing targeted therapies against CRC.
METHODS: The purpose of this study was to analyze in silico the differentially expressed genes from five microarray datasets of patients with CRC. Furthermore, miRNAs were investigated to inhibit cancer cell proliferation and metastasis by targeting a key gene-frizzled receptor 3 (FZD3) in the Wnt signaling pathway.
RESULTS: The Wnt pathway receptor FZD3 is upregulated in CRC along with other pathway genes, which play a critical role in tumorigenesis. In contrast, miR-98-5p inhibits the activity of FZD3 by binding directly to the 3\'UTR of its mRNA, therefore exerting a suppressor effect on colorectal tumors.
CONCLUSIONS: The study reveals miR-98-5p as a novel target of FZD3 and an inhibitor of the Wnt signaling pathway hence being a potential candidate for developing targeted therapies against CRC.
摘要：
背景：结直肠癌（CRC）是全球第三常见的癌症类型，也是导致癌症相关死亡的第二大原因。然而,现有的治疗方法,以及CRC患者的预后策略，需要改进，以增加生存的机会。CRC的靶向治疗，与普通疗法相反，靶向癌细胞的关键生物学特征和途径，从而最大限度地减少对正常细胞的后续损害。已经报道微RNA通过靶向这些途径中的关键基因的转录物在抑制和/或抑制各种癌症类型的主要途径中起关键作用。
方法：本研究的目的是分析来自5个CRC患者微阵列数据集的差异表达基因。此外，研究了通过靶向Wnt信号通路中的关键基因卷曲受体3(FZD3)来抑制癌细胞增殖和转移的miRNA。
结果：在CRC中Wnt通路受体FZD3与其他通路基因一起上调，在肿瘤发生中起关键作用。相比之下,miR-98-5p通过直接结合其mRNA的3'UTR抑制FZD3的活性,因此对结肠直肠肿瘤有抑制作用。
结论：该研究揭示miR-98-5p作为FZD3的新靶标和Wnt信号通路的抑制剂，因此是开发针对CRC的靶向治疗的潜在候选者。
方法：本研究的目的是分析来自5个CRC患者微阵列数据集的差异表达基因。此外，研究了通过靶向Wnt信号通路中的关键基因卷曲受体3(FZD3)来抑制癌细胞增殖和转移的miRNA。
结果：在CRC中Wnt通路受体FZD3与其他通路基因一起上调，在肿瘤发生中起关键作用。相比之下,miR-98-5p通过直接结合其mRNA的3'UTR抑制FZD3的活性,因此对结肠直肠肿瘤有抑制作用。
结论：该研究揭示miR-98-5p作为FZD3的新靶标和Wnt信号通路的抑制剂，因此是开发针对CRC的靶向治疗的潜在候选者。
