The gain and loss of long noncoding RNA associated-competing endogenous RNAs in prostate cancer

Abstract

Prostate cancer (PC) is one of the most common solid tumors in men. However, the molecular mechanism of PC remains unclear. Numerous studies have demonstrated that long noncoding RNA (lncRNA) can act as microRNA (miRNA) sponge, one type of competing endogenous RNAs (ceRNAs), which offers a novel viewpoint to elucidate the mechanisms of PC. Here, we proposed an integrative systems biology approach to infer the gain and loss of ceRNAs in PC. First, we re-annotated exon microarray data to obtain lncRNA expression profiles of PC. Second, by integrating mRNA and miRNA expression, as well as miRNA targets, we constructed lncRNA-miRNA-mRNA ceRNA networks in cancer and normal samples. The lncRNAs in these two ceRNA networks tended to have a longer transcript length and cover more exons than the lncRNAs not involved in ceRNA networks. Next, we further extracted the gain and loss ceRNA networks in PC. We found that the gain ceRNAs in PC participated in cell cycle, and the loss ceRNAs in PC were associated with metabolism. We also identified potential prognostic ceRNA pairs such as MALAT1-EGR2 and MEG3-AQP3. Finally, we inferred a novel mechanism of known drugs, such as cisplatin, for the treatment of PC through gain and loss ceRNA networks. The potential drugs such as 1,2,6-tri-O-galloyl-beta-D-glucopyranose (TGGP) could modulate lncRNA-mRNA competing relationships, which may uncover new strategy for treating PC. In summary, we systematically investigated the gain and loss of ceRNAs in PC, which may prove useful for identifying potential biomarkers and therapeutics for PC.

LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer

“…In addition, in our study, HOTAIR overexpression was found to be positively correlated with advanced histological grade, FIGO stage and extensive metastasis, indicating that HOTAIR was an excellent biomarker for the prognosis of ovarian cancer and that the downregulation of HOTAIR may arrest tumor progression and inhibit the metastatic phenotype. Currently, the lncRNA-miRNA-mRNA regulatory network is widely recognized; in this network, lncRNA acts as a natural miRNA sponge (ceRNA) to sponge miRNAs, thus decreasing the expression of miRNA targets and affecting posttranscriptional regulation [32]. For example, it is reported that lncRNA PTENP1 functioned as a ceRNA to modulate PTEN levels by decoying miR-106b and miR-93 in gastric cancer [33].…”

Integrated analysis of dosage effect lncRNAs in lung adenocarcinoma based on comprehensive network

“…Recent studies verified that miRNAs was useful for lncRNA analysis [ 52 – 54 ]. For example, lncRNAs could act as miRNA sponges to regulate the expression of other transcripts [ 55 ]. In order to evaluate the ceRNA interactions that were mediated by lncRNAs, we constructed the lncRNA-miRNA-mRNA ceRNA network through a multi-step method ( Supplementary Figure S4 ).…”

Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients

“…Furthermore, functional genomic analyses were designed to provide a potential biological basis for the observed associations. Rs10132552 polymorphisms could create miRNA (mir-564, mir-650 and mir-602) binding sites on MEG3 , disturbing the lncRNA-miRNA interaction, acting as competing endogenous RNAs (ceRNA) and thereby negatively regulating miRNA expression 36 , 37 . Interestingly, it is clear that mir-650, mir-602 and mir-564 played roles in cancers such as breast cancer and lung cancer 38 – 40 .…”