Kenneth Mutebi John, Shishir Tushar Ahmed, Haque Fahim Kabir Monjurul
Biotechnology Program, Department of Mathematics and Natural Sciences, BRAC University, Mohakhali, 1212, Dhaka, Bangladesh.
Microbiology Program, Department of Mathematics and Natural Sciences, BRAC University, Mohakhali, 1212, Dhaka, Bangladesh.
J Genet Eng Biotechnol. 2023 Jul 19;21(1):79. doi: 10.1186/s43141-023-00532-7.
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.
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.
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.
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.
结直肠癌(CRC)是全球第三大常见癌症类型,也是癌症相关死亡的第二大主要原因。然而,现有的治疗方法以及CRC患者的预后策略需要改进,以提高生存率。与普通疗法不同,CRC的靶向疗法针对癌细胞的关键生物学特征和途径,从而将对正常细胞的后续损害降至最低。据报道,微小RNA通过靶向各种癌症类型中关键基因的转录本,在抑制和/或阻断主要途径中发挥关键作用。
本研究的目的是通过计算机分析来自CRC患者的五个微阵列数据集的差异表达基因。此外,研究了微小RNA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。
Wnt通路受体FZD3在CRC中与其他通路基因一起上调,这些基因在肿瘤发生中起关键作用。相反,miR-98-5p通过直接与其mRNA的3'UTR结合来抑制FZD3的活性,从而对结直肠肿瘤发挥抑制作用。
该研究揭示了miR-98-5p是FZD3的新靶点以及Wnt信号通路的抑制剂,因此是开发针对CRC的靶向疗法的潜在候选者。