Pancreatic ductal adenocarcinoma (PDAC) the most lethal cancer due to its late diagnosis, high rate of metastasis and drug resistance. Therefore, the discovery of novel molecular targets is an urgent need. The aim of this study is to delineate the potential of SNHG10 in PDAC.

Bioinformatic and qRT-PCR analysis was used to determine the expression of SNHG10. Antisense oligonucleotide and siRNA mediated approach were utilized to unravel SNHG10 role using MTT, clonogenic assay, boyden chamber assay, cell cycle and apoptosis assay. Mechanism of SNHG10 was discovered through western blot analysis. NOD-SCID mice model of PDAC validated the in vitro analysis. Immunohistochemical analysis was used to analyze the altered expression of key oncogenic protein. Furthermore, SNHG10 involvement in gemcitabine resistance was evaluated by developing gemcitabine resistance PDAC cell lines.

Our analysis displayed a significant upregulation of SNHG10 transcript in 179 PDAC cases and in a panel of PDAC cell lines. Upregulation of SNHG10 showed correlation with clinical stages of PDAC. Depletion of SNHG10 transcript level displayed significant reduction in cell proliferation, clonogenic ability, cell migration, EMT while inducing cell cycle arrest and cell death of PDAC cells. Mechanistically, the depletion of SNHG10 inhibited protein expression of cyclinB1, CDK4, cyclin D1, CDK6, N-cadherin, vimentin, survivin, aurora Kinase A & B. The depletion of SNHG10 led to enhanced expression of p21 and E-cadherin in PDAC cells. Moreover, depletion of SNHG10 significantly suppressed the tumor growth in PDAC xenograft model. Silencing of SNHG10 increased the expression of miR-532-3p and miR-150-5p leading to inhibition of EGFR/AKT/ERK/mTOR/MET signaling in both in vitro and xenograft PDAC mouse model. Noticeably, silencing of SNHG10 transcript increases the gemcitabine sensitivity of PDAC cells resistant to gemcitabine.

Our data indicated the oncogenic role of SNHG10 in PDAC through the EGFR/AKT/ERK1/2/mTOR axis as well as involved in gemcitabine resistance.