Multi-omics data integration reveals the molecular network of dysregulation IQGAP2-mTOR promotes cell proliferation

IQGAP2 as a tumor suppressor gene can influence cell proliferation in multiple tumor cell lines. However, the regulation network of cell proliferation resulting solely from the deficiency of IQGAP2 in cells was still unclear. Here, we integrated transcriptome, proteome, and phosphoproteome analyses to investigate the regulatory network of cell proliferation in IQGAP2 knockdown HaCaT and HEK293 cells. Our findings revealed that the dysregulation of the IQGAP2-mTOR molecular network led to increased cell proliferation. We demonstrated that IQGAP2 knockdown enhanced the phosphorylation levels of AKT and S6K, leading to increased cell proliferation. Additionally, we found that AKT and mTOR inhibitors partially rescued abnormal cell proliferation by reducing hyperphosphorylation. Our data suggest a potential connection between the mTOR signaling pathway and aberrant cell proliferation in IQGAP2 knockdown cells. These findings offer a new therapeutic strategy for patients with IQGAP2 deficiency.

Automated summary

As a tumor suppressor gene, IQGAP2 can affect cell proliferation in multiple tumor cell lines. However, the regulation network of cell proliferation caused by the deficiency of IQGAP2 in cells is still unclear. In this study, we used transcriptome, proteome, and phosphoproteome analyses to investigate the regulatory network of cell proliferation in IQGAP2 knockdown HaCaT and HEK293 cells. Our findings suggest that the dysregulation of the IQGAP2-mTOR molecular network leads to increased cell proliferation. We also demonstrated that IQGAP2 knockdown enhances the phosphorylation levels of AKT and S6K, resulting in increased cell proliferation. Additionally, inhibition of AKT and mTOR partially rescues abnormal cell proliferation by reducing hyperphosphorylation. These results indicate a potential connection between the mTOR signaling pathway and aberrant cell proliferation in IQGAP2 knockdown cells, providing a new therapeutic strategy for patients with IQGAP2 deficiency.