In silico analysis reveals mir-98-5p as a potential inhibitor of tumor cell proliferation and metastasis in colorectal cancer by targeting the fzd3 receptor of the Wnt signaling pathway

Mutebi John Kenneth; Tushar Ahmed Shishir; Fahim Kabir Monjurul Haque

doi:10.1186/s43141-023-00532-7

In silico analysis reveals mir-98-5p as a potential inhibitor of tumor cell proliferation and metastasis in colorectal cancer by targeting the fzd3 receptor of the Wnt signaling pathway

J Genet Eng Biotechnol. 2023 Jul 19;21(1):79. doi: 10.1186/s43141-023-00532-7.

Authors

Mutebi John Kenneth¹, Tushar Ahmed Shishir¹, Fahim Kabir Monjurul Haque²

Affiliations

¹ Biotechnology Program, Department of Mathematics and Natural Sciences, BRAC University, Mohakhali, 1212, Dhaka, Bangladesh.
² Microbiology Program, Department of Mathematics and Natural Sciences, BRAC University, Mohakhali, 1212, Dhaka, Bangladesh. fahim.haque@bracu.ac.bd.

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.

Conclusion: 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.

Keywords: Colorectal cancer; Frizzled receptors; MicroRNAs; WNT pathway; miR-98-5p.