Molecular mechanism of AQP3 in regulating differentiation and apoptosis of lung cancer stem cells through Wnt/GSK-3ß/ß-Catenin pathway.

ABSTRACT

PURPOSE: The refractory nature and proneness to recurrence of lung cancer are related to the proliferation and differentiation of lung cancer stem cells (LCSCs). This paper aims to explore the effect of aquaporin-3 (AQP3) on the functions of LCSCs, and its molecular mechanism in regulating the differentiation and apoptosis of LCSCs through the Wnt/glycogen synthase kinase-3ß (GSK-3ß)/ß-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 the control group and transfected with AQP3 shRNA in the interference group, and the low expression of AQP3 was inhibited using the Wnt pathway inhibitor XAV939 in the interference+inhibitor group. The expressions of AQP3, Wnt/GSK-3ß/ß-catenin pathway genes, stemness genes, differentiation-related markers and apoptosis proteins in LCSCs were detected. RESULTS: In the interference group, the pathway genes were highly expressed. The genes in the interference group were enriched in the Wnt/GSK-3ß/ß-catenin pathway. In the interference group, the expressions of ß-catenin, GSK-3ß 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 the interference group, the expressions of stemness-related genes were obviously higher, while the expression of CDK2 had no difference (p=0.471). The interference group had higher expressions of differentiation markers. CONCLUSION: AQP3 can reduce the differentiation and inhibit the apoptosis of LCSCs through reducing the expressions of Wnt/GSK-3ß/ß-catenin pathway-related genes such as ß-catenin, GSK-3ß and STAT3, thereby affecting the tumor progression.