SNHG10 promote tumorigenesis via miR-150/VEGFA/EGFR/AKT/ERK/mTOR axis and gemcitabine resistance in PDAC

Abstract

SNHG10 emerged as a key regulator in progression and metastasis of cancers. However, potential of SNHG10 in PDAC tumorigenesis, gemcitabine resistance, and underlying mechanisms remains poorly understood. We observed significant upregulation of SNHG10 in 179 PDAC cases, revealing a positive correlation with clinical stages. Our results showed a significant SNHG10 overexpression in several PDAC cells. Downregulation of SNHG10 significantly decreased the proliferation, clonogenicity, EMT, tumor growth in the xenograft model, and the induction of cell cycle arrest and apoptosis of PDAC cells. Mechanistically, SNHG10 knockdown significantly inhibited the expression of vimentin, N-cadherin, survivin, CDK4, CDK6, cyclin B1, cyclin D1, aurora kinase A, and B, with an increased expression of E-cadherin and p21. RNA Immunoprecipitation data displayed physical interaction among SNHG10, miR-150-5p, and VEGFA in PDAC cells. SNHG10 silencing led to the significant induction of miR-150-5p, which repressed VEGFA expression in PDAC cells. SNHG10 downregulation enhanced gemcitabine sensitivity in PDAC cells. SNHG10 silencing suppressed the phosphorylation of EGFR, AKT, ERK1/2, mTOR, and c-MET pathways. Silencing SNHG10 and its regulated signalling offers a novel prospective therapeutic strategy.