The Role Of LncRNA PAUPAR In Ocular Melanoma Tumorigenesis And A Preliminary Clinical Study

Objective Uveal melanoma(Uveal Melanoma,UM)is the most common primary intraocular tumour in adults and has a high incidence.Patients with UM develop metastases after diagnosis and the metastatic disease is universally fatal and no effective systemic therapies are currently available.The role of genetic cause is the main mechanism in UM,besides,epigenetics play an important role in UM tumorigenesis.Long non-coding RNAs(lnc RNAs)are emerging as players in the cancer paradigm,exhibiting potential roles in both oncogenic and tumour suppression pathways.Here we aim to identify the relationship between lnc RNAPAUPAR and UM tumorigenesis,additionally explore the function and mechanism of lnc RNA in tumorigenesis.It is hard to identify the corneal and conjunctival pigmented nevus neoplasm on the basis of clinical history.The analysis of the corresponding pathology characteristics of patients contributed to the diagnosis and treatment of ocular surface pigmented nevus neoplasm.Content and methods 1.Differentially expressed lnc RNA PAUPAR in UM tissues and cell lines was identified.2.MTT,Colony formation,Transwell assay and Xenograft model assay were performed to estimate the influence of lnc RNA on tumor characters.3.The target gene was filtrated by Real-time PCR.4.RNAi and Transwell assay were performed to demonstrate the functions of the target gene on tumor progress.5.PAUPAR localization and Chromatin Immunoprecipitation were utilized to investigate the underlying mechanism of lnc RNA PAUPAR in UM.6.Retrospective analysis was performed on 55 patients with pigmented nevus neoplasm.Conclusions 1.PAUPAR levels are low in UM tissues and cell lines and PAUPAR suppresses the tumourigenesis of UM in vitro and in vivo.2.HES1 serves as a target of PAUPAR and si RNA targeting HES1 weakens the cell migratory ability in UM cells.3.PAUPAR lnc RNA modulates HES1 expression by regulating histone H3K4 methylation to regulate UM.4.Understand the clinical features and histopathological characteristics of the corneal and conjunctival pigmented nevus neoplasm.Achievements 1.We demonstrate PAUPAR serves as a tumor suppressor in UM.2.We make it clear that HES1 serves as a target of PAUPAR and its impact on the biological characteristics of UM.3.We reveal the regulatory mechanism of PAUPAR and its target gene HES1 4.The analysis of the corresponding pathology characteristics contributed to the diagnosis and treatment of ocular surface pigmented nevus neoplasm.