WISP1 indicates poor prognosis and regulates cell proliferation and apoptosis in gastric cancer via targeting AKT/mTOR signaling pathway

Am J Transl Res. 2020 Nov 15;12(11):7297-7311. eCollection 2020.

ABSTRACT

PURPOSE: Gastric cancer (GC) is a serious threat to human health. We aimed to explore the effects of Wnt1 induced signaling protein 1 (WISP1) on GC.

METHODS: The WISP1 expressions in GC tissues were detected using immunohistochemistry and qRT-PCR. The connection between GC prognosis and WISP1 expression was analyzed via Pearson's χ² test. The WISP1 expressions were down-regulated in GC cells through siWISP1 transfection. Colony formation assay and cell counting kit-8 assay were carried out to measure cell colony formation and proliferation, respectively. Flow cytometry was operated to examine the cell cycle and apoptosis. The protein expressions in our study were assessed using western blot. The AKT pathway was blocked by LY294002 treatment and then the cell activities were assessed. Furthermore, GC mice models were established to investigate the effects of WISP1 on GC in vivo.

RESULTS: We found that WISP1 was highly expressed in GC cells and tissues. The up-regulation of WISP1 was related to poor prognosis of GC patients. WISP1 down-regulation reduced colony formation and cell proliferation, resulted cell cycle arrest and promoted cell apoptosis in GC. WISP1 knockdown suppressed AKT/mTOR pathway activity. LY294002 treatment recovered the decreases of colony formation and cell proliferation, arrest of cell cycle and increase of cell apoptosis which were induced by WISP1 knockdown. WISP1 down-regulation repressed GC tumor growth and enhanced tumor apoptosis in vivo.

CONCLUSION: WISP1 regulated GC cell proliferation and apoptosis in vivo and in vitro through activating AKT/mTOR pathway. WISP1 might be a target in GC therapy.

PMID:33312368 | PMC:PMC7724330