Glucosidase GANAB drives colorectal cancer progression through Wnt signaling and is modulated by lncRNA FIRRE.

BACKGROUND

The goal of this study is to investigate the expression pattern of GANAB in colorectal cancer and the role behind it.

METHODS

In order to study the expression level of GANAB in the tissue of colorectal cancer, we used quantitative real-time PCR and immunohistochemistry. In the aspect of biological function, we study it through the experimental models. The molecular mechanism is clarified by RNA pull-down and RNA stability assays. Student's t-tests and one-way ANOVA are used for data analysis.

RESULTS

Analysis of tissue microarrays and Colorectal cancer (CRC) cell lines revealed elevated GANAB expression in tumors compared to normal counterparts. Increased GANAB levels were linked to enhanced cell migration, invasion, and proliferation, and correlated with metastatic potential and unfavorable patient outcomes. Functional enrichment studies indicated that GANAB-associated genes participate in the Wnt/β-catenin signaling pathway. Immunohistochemistry confirmed positive correlations between GANAB and both c-Myc and β-catenin. The oncogenic function of GANAB was shown to rely on Wnt pathway activation. Additionally, lncRNA FIRRE, known to be oncogenic in CRC, was found to physically interact with GANAB mRNA via RNA pull-down assays. FIRRE enhances GANAB mRNA stability through direct binding.

CONCLUSION

Our study demonstrates that GANAB exerts oncogenic effects in CRC by binding directly to lncRNA FIRRE, thereby stabilizing GANAB mRNA and activating the Wnt/β-catenin pathway through nuclear accumulation of β-catenin.