SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling.

Abstract

In our prior research, it was noted that slit guidance ligand 3 (SLIT3), a member of the SLIT-secreted protein family, may play a potential role in tumorigenesis. In addition, our prior work has found that the SLIT3 gene is highly methylated, especially in advanced-stage lung cancer tissues. Herein, we propose the hypothesis that abnormal SLIT3 expression may be linked to lung cancer development. In this study, decreased SLIT3 at the transcriptome and proteome levels was observed in lung cancer tissues. Furthermore, the downregulation of SLIT3 was related to a higher tumor stage and poorer prognosis. Silencing SLIT3 expression enhanced cell proliferation and migration, indicating potential characteristics of a tumor suppressor gene of SLIT3 in non-small-cell lung cancer (NSCLC). Furthermore, SLIT3 deficiency stimulates UBE2C upregulation and regulates NSCLC progression through Wnt3A/β-catenin signaling. The activation of the WNT signaling pathway was highly correlated with chemoresistance development in lung cancer. In conclusion, SLIT3 deficiency promotes lung cancer onset and progression by modulating UBE2C/WNT signaling. SLIT3/UBE2C/WNT may serve as novel biomarkers and therapeutic targets in NSCLC.