Purpose: To explore the effect of aquaporin-3 (AQP3) on the functions of lung cancer stem cells (LCSCs), and its molecular mechanism in regulating the differentiation and apoptosis of LCSCs through the Wnt/glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway.
Methods: The stem cells were selected and the cell lines with low expression of AQP3 were constructed, followed by transcriptome sequencing. LCSCs were transfected with empty lentivirus in control group and transfected with AQP3 shRNA in interference group, and the low expression of AQP3 was inhibited using the Wnt pathway inhibitor XAV939 in interference + inhibitor group. The expressions of AQP3, Wnt/GSK-3β/β-catenin pathway genes, stemness genes, differentiation-related markers and apoptosis proteins in LCSCs were detected.
Results: In interference group, the pathway genes were highly expressed. The genes in interference group were enriched in the Wnt/GSK-3β/β-catenin pathway. In interference group, the expressions of β-catenin, GSK-3β and signal transducer and activator of transcription 3 (STAT3) were significantly higher, while the expression of adenomatous polyposis coli (APC) was significantly lower (p<0.05). The expression of Wnt5α had no difference. In interference group, the expressions of stemness-related genes were obviously higher, while the expression of CDK2 had no difference (p=0.471). Interference group had higher expressions of differentiation markers.
Conclusion: In conclusion, AQP3 can reduce the differentiation and inhibit the apoptosis of LCSCs through reducing the expressions of Wnt/GSK-3β/β-catenin pathway-related genes such as β-catenin, GSK-3β and STAT3, thereby affecting the tumor progression.