Identification of Potential Prostate Cancer-Related Pseudogenes Based on Competitive Endogenous RNA Network Hypothesis
Tao Jiang, Junjie Guo, Zhongchun Hu, Ming Zhao, Zhenggang Gu, Shu Miao
Department of Urology, Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland)
Med Sci Monit 2018; 24: LBR4213-4239
Available online: 2018-06-20
Long noncoding RNAs (lncRNAs) have been revealed to function as competing endogenous RNAs (ceRNAs), which can seclude the common microRNAs (miRNAs) and hence prevent the miRNAs from binding to their ancestral gene. Nonetheless, the role of lncRNA-mediated ceRNAs in prostate cancer has not yet been elucidated.
MATERIAL AND METHODS: Using The Cancer Genome Atlas (TCGA) database, lncRNA, miRNA, and mRNA profiles from 499 prostate cancer tissues and 52 normal prostate tissues were analyzed with the R package “DESeq” to identify the differentially expressed RNAs. GO and KEGG pathway analyses were performed using “DAVID6.8” and R packages “Clusterprofile.” The ceRNA network in prostate cancer was constructed using miRDB, miRTarBase, and TargetScan databases. Survival analysis was performed with Kaplan-Meier analysis.
RESULTS: A total of 376 lncRNAs, 33 miRNAs, and 687 mRNAs were identified as significant factors in tumorigenesis. Based on the hypothesis that the ceRNA network (lncRNA-miRNA-mRNA regulatory axis) is involved in prostate cancer and forms competitive interrelations between miRNA and mRNA or lncRNA, we constructed a ceRNA network that included 23 lncRNAs, 6 miRNAs, and 2 mRNAs that were differentially expressed in prostate cancer. Only 3 lncRNAs (LINC00308, LINC00355, and OSTN-AS1) had a significant association with survival (P<0.05). The 3 prostate cancer-specific lncRNA were validated in prostate cancer cell lines PC3 and DU145 using qRT-PCR.
CONCLUSIONS: We demonstrated the differential lncRNA expression profiles in prostate cancer, which provides new insights for future studies of the ceRNA network and its regulatory mechanisms in prostate cancer.
Keywords: carcinogenesis, Prostatic Neoplasms, RNA, Long Noncoding