Knockdown of lncRNA PVT1 inhibits prostate cancer progression in vitro and in vivo by the suppression of KIF23 through stimulating miR-15a-5p

Huijuan Wu,Xin Tian,Chaoyang Zhu

doi:10.1186/s12935-020-01363-z

Huijuan Wu, Xin Tian + Show 1 more

Open Access

https://doi.org/10.1186/s12935-020-01363-z

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Abstract

BackgroundProstate cancer (PCa) greatly threatens men’s lives, with high incidence and mortality. Recently, the research of long non-coding RNAs (lncRNAs) has made breakthroughs in the development of human cancers. This study aimed to figure out the role and action mechanism of lncRNA PVT1 (PVT1) in PCa.MethodsThe expression of PVT1, microRNA-15a-5p (miR-15a-5p) and kinesin family member 23 (KIF23) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assays, respectively. The protein levels of KIF23 and proliferation, apoptosis, and epithelial-mesenchymal transition (EMT)-related markers were quantified by western blot. The relationship between miR-15a-5p and PVT1 or KIF23 was predicted by starBase v2.0 and verified by dual-luciferase reporter assay. Xenograft assay was conducted to determine the role of PVT1 in vivo.ResultsThe expression of PVT1 and KIF23 was enhanced, while miR-15a-5p expression was reduced in PCa tissues and cells. PVT1 interference inhibited proliferation, migration and invasion but promoted apoptosis of PCa cells. MiR-15a-5p was a target of PVT1, and KIF23 was a target of miR-15a-5p. The inhibition of miR-15a-5p reversed the effects of PVT1 interference and suppressed the roles of KIF23 knockdown. KIF23 expression was regulated by PVT1 through miR-15a-5p. PVT1 interference blocked PCa progression in vivo.ConclusionPVT1 knockdown had effects on the progression of PCa by inhibiting the expression of KIF23 via enriching miR-15a-5p in vitro and in vivo, suggesting that PVT1 might be a novel biomarker for the treatment of PCa.

Highlights

Prostate cancer (PCa) greatly threatens men’s lives, with high incidence and mortality
Plasmacytoma Variant Translocation 1 (PVT1) and kinesin family member 23 (KIF23) are up-regulated, while miR-15a-5p is down-regulated in PCa tissues and cells
Whereafter, the expression of PVT1, miR-15a-5p and KIF23 was detected in removed tumor tissues, and we found the expression of PVT1 and KIF23 was significantly declined, while miR-15a-5p expression was strengthened by quantitative real-time polymerase chain reaction (qRT-PCR) analysis (Fig. 7c)

Summary

Introduction

Prostate cancer (PCa) greatly threatens men’s lives, with high incidence and mortality. This study aimed to figure out the role and action mechanism of lncRNA PVT1 (PVT1) in PCa. Prostate cancer (PCa), a common malignancy in the male population, is an important cause of male mortality [1]. The complex mechanism of PCa initiation and development involves various factors, such as age, lifestyle, environment, and heredity [1, 4]. Androgen deprivation therapy is the mainstream method for the treatment of PCa and has a considerable curative effect in the early stage [5, 6]. Inappropriate screening schedules, low cure rates, and drug resistance are substantial burdens in the treatment of PCa [1]. The underlying mechanisms associated with the development and progression of PCa and novel targeted specific biomarkers still require further investigation

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