Abstract
BackgroundChemo-resistance is one of the main obstacles in the treatment of prostate cancer (PCa). Long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) is involved in the chemo-resistance of various tumors. We aim to survey the role and underlying molecular mechanism of SNHG6 in PCa resistance to paclitaxel (PTX).MethodsThe expression of SNHG6 and miR-186 was detected using quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, and apoptosis of PTX-resistant PCa cells were determined via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), transwell assay, or flow cytometry assay. Protein levels of CyclinD1, matrix metalloproteinase 9 (MMP9), Vimentin, E-cadherin, Cleaved-caspase-3 (Cleaved-casp-3) Cleaved-caspase-9 (Cleaved-casp-9), Multidrug Resistance associated Protein 1 (MRP1), and multidrug resistance-1 (MDR1) were assessed by western blot analysis. The relationship between SNHG6 and miR-186 were confirmed by dual-luciferase reporter assay. The role of SNHG6 in vivo was confirmed by xenograft tumor model.ResultsSNHG6 expression was increased and miR-186 expression was reduced in drug-resistant PCa tissues and cells. SNHG6 knockdown elevated PTX-resistant PCa cells sensitivity to PTX in vitro and in vivo, and repressed proliferation, migration, and invasion of PTX-resistant PCa cells in vitro. Importantly, SNHG6 acted as a sponge of miR-186. Furthermore, miR-186 downregulation reversed SNHG6 silencing-mediated cell sensitivity to PTX, proliferation, migration, and invasion in PTX-resistant PCa cells.ConclusionsSNHG6 knockdown elevated the sensitivity of PTX-resistant PCa cells to PTX by sponging miR-186, indicating that SNHG6 might be a therapeutic target for PCa.
Highlights
Chemo-resistance is one of the main obstacles in the treatment of prostate cancer (PCa)
small nucleolar RNA host gene 6 (SNHG6) knockdown elevated the sensitivity of PTX-resistant PCa cells to PTX by sponging miR-186, indicating that SNHG6 might be a therapeutic target for PCa
SNHG6 was elevated while miR‐186 was reduced in drug‐resistant PCa tissues and cells In order to explore the relevance of SNHG6 in the chemo-resistance of PCa, we determined the expression pattern of SNHG6 and miR-186 in 30 drug-sensitivity PCa tissues and 33 drug-resistant PCa tissues by qRTPCR
Summary
Chemo-resistance is one of the main obstacles in the treatment of prostate cancer (PCa). Long noncoding RNA small nucleolar RNA host gene 6 (SNHG6) is involved in the chemo-resistance of various tumors. We aim to survey the role and underlying molecular mechanism of SNHG6 in PCa resistance to paclitaxel (PTX). About 25% of PCa patients relapse within 5 years, and the recurrence of PCa and progression of castration-resistant are the main causes of PCa death [2, 3]. PTX is the first-line treatment drug for PCa. the main cause of recurrence in PCa patients is resistance to PTX [4].
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