CircNOLC1 Regulates Prostate Cancer Progress By MiR-647/PAQR4 Axis

BackgroundProstate Cancer is currently one of the most common urinary system cancers worldwide.Although surgery and castration can treat some prostate cancers,some continue to recur and develop malignantly,therefore,it is necessary to find new potential targets for the prognosis and treatment of prostate cancer.Recently,studies have shown that circular RNA(Circular RNA,CircRNA)is abnormally expressed in a variety of tumors,and plays an important role in regulating tumorigenesis and the development of tumors,but its pathological mechanism for regulating the progression of prostate cancer remains to be revealed.The purpose of this research is to study the cellular and biological functions of circNOLC1 in the prostate cancer and to elucidate its mechanism in the progression of prostate cancer.MethodsCircRNA microarrays were used to sequence the immortalized prostate epithelial cell line RWPE1 and the prostate cancer cell lines DU 145,PC3,LNCaP,C4-2 and 22RV1.Combined with the up-regulated circRNAs in prostate cancer tissue,the expression level of circNOLC1 in prostate cancer tissues and cells was confirmed by qRT-PCR and FISH.Next,Sanger sequencing,actinomycin D RNA stability and RNase R asssays were used to determine the circular characteristics of circNOLC1.CCK-8,Clony formation,wound healing assay,transwell migration assays and mouse xenograft model were applied to validate the function of circNOLC1 in PCa after circNOLC1 knockdown and overexpression.What's more,RNA pulldown,dual luciferase reporter assay,FISH,chromatin immunoprecipitation(CHIP)and bioinformatics analasis were utilized to further explore the specific mechanism of circNOLC1.ResultsOur investigations indicated that the expression level of circNOLC1 was significantly up-regulated in prostate tumor tissues and cells,and circNOLC1 was more stable than the mRNA of its linear host gene NOLC1.Experiments in vivo and in vitro had proved that circNOLC1 promoted the proliferation and metastasis of prostate cancer cells.In addition,we found that circNOLC1 can upregulate PAQR4 expression by sponging miR-647,resulting in the activation of the PI3K/Akt signaling pathway.Moreover,NF-kappaB was identified to bind to the NOLC1 promoter sites and upregulated the expression of NOLC1 and circNOLC1.ConclusionCircNOLC1,upregulated by the transcription factor NF-kappaB,can promote prostate cancer progression through the miR-647/PAQR4 signal axis.In conclusion,this study revealed the key role of circNOLC1 in promoting the proliferation and metastasis of prostate cancer,and may be function as a potential biomarker and target for the treatment of prostate cancer.