Long Noncoding RNAs LncRNA-THBS4-003 Involves In Migration And Invasion In Prostate Cancer Cell Lines

BACKGROUND.Increasing evidence implicates long noncoding RNAs(lnc RNAs),a class of noncoding RNAs greater than 200 nucleotides in length,in cancer development.However,the mechanism of lnc RNAs in prostate cancer(PCa)is unclear.This study aims to investigate the role of lnc RNA-THBS4-003 in prostate cancer(PCa)pathogenesis.METHODS.In this study,a microarray containing 8277 lnc RNA probes and 32207 m RNA probes was used to identify dysregulated m RNAs in three PCa patients,and quantitative real-time polymerase chain reaction(q RT-PCR)was used to demonstrate the expression of Thrombospondin-4(THBS4)and lnc RNA-THBS4-003 in 46 primary PCa and adjacent non-tumor tissue samples.The expression levels of THBS4 were determined in six samples of PCa and adjacent non-tumor tissues by Western blot analysis.The effects of forced THBS4 knockdown or lnc RNA-THBS4-003 knockdown on 2 PCa cell lines,including DU145 and PC-3,were evaluated using cell migration and invasion assays,as well as by Western blot analysis.RESULTS.Of the 40484 probes on the microarray,354 were significantly upregulated(P<0.05;FC>2).The most significantly upregulated m RNA was THBS4.The expression of both THBS4 and lnc RNA-THBS4-003 in the 46 primary PCa samples was significantly higher compared with that in the adjacent non-tumor tissue samples.Patients with Gleason scores >7 exhibited higher lnc RNA-THBS4-003 expression levels than those with lower scores.Knockdown of THBS4 or lnc RNA-THBS4-003 significantly reduced the migratory and invasive abilities of PCa cells in vitro and decreased the expression of P38 and MMP-9.CONCLUSIONS.Our findings suggest that the reciprocal regulation of lnc RNA-THBS4-003 and THBS4 contributes to PCa pathogenesis.Silencing lnc RNA-THBS4-003 or THBS4 could inhibit PCa cell migration and invasion andregulate MMP-9 levels through the MAPK signaling pathway.