Five Circular RNAs in Metabolism Pathways Related to Prostate Cancer

Abstract

Prostate cancer (PCa) is the most common malignant tumor in men, and its incidence increases with age. Serum prostate-specific antigen and tissue biopsy remain the standard for diagnosis of suspected PCa. However, these clinical indicators may lead to aggressive overtreatment in patients who have been treated sufficiently with active surveillance. Circular RNAs (circRNAs) have been recently recognized as a new type of regulatory RNA that is not easily degraded by RNases and other exonucleases because of their covalent closed cyclic structure. Thus, we utilized high-throughput sequencing data and bioinformatics analysis to identify specifically expressed circRNAs in PCa and filtered out five specific circRNAs for further analysis—hsa_circ_0006410, hsa_circ_0003970, hsa_circ_0006754, hsa_circ_0005848, and a novel circRNA, hsa_circ_AKAP7. We constructed a circRNA-miRNA regulatory network and used miRNA and differentially expressed mRNA interactions to predict the function of the selected circRNAs. Furthermore, survival analysis of their cognate genes and PCR verification of these five circRNAs revealed that they are closely related to well-known PCa pathways such as the MAPK signaling pathway, P53 pathway, androgen receptor signaling pathway, cell cycle, hormone-mediated signaling pathway, and cellular lipid metabolic process. By understanding the related metabolism of circRNAs, these circRNAs could act as metabolic biomarkers, and monitoring their levels could help diagnose PCa. Meanwhile, the exact regulatory mechanism for AR-related regulation in PCa is still unclear. The circRNAs we found can provide new solutions for research in this field.

Differentially expressed AC077690.1, AL049874.3 and AP001037.1 lncRNAs in prostate cancer

“…Differentially expressed lncRNAs must be identified and verified in many samples. In the present study, which was based on the sequencing data of PCa tissues and adjacent normal tissues reported in our previous study [16], we identified several differentially expressed lncRNAs. Among the top 10 abnormally high-expressed lncRNAs, we focused on three PCarelated lncRNAs, namely AC077690.1, AL049874.3 and AP001037.1.…”

“…For sequencing samples, two pairs of PCa tissues and adjacent tissues were obtained from surgical samples. The RNA library's detailed sample information and construction were described in our previous research [16]. For quantitative real-time polymerase chain reaction(qRT-PCR), 10 pairs of PCa tissues and adjacent normal tissues with Gleason scores of 7 were obtained from the Department of Pathology of Beijing Hospital.…”

“…In our previous research, we sequenced six sets of RNA-seq obtained from four PCa tissues and two adjacent normal tissues from two patients [16]. Comparing sequencing data, we obtained differentially expressed lncRNAs.…”

Circular RNAs Modulate Cancer Hallmark and Molecular Pathways to Support Cancer Progression and Metastasis

“…Similarly, circRNAs have also been found to participate in modulating the energy metabolism in cancer cells. For instance, Zhang et al recently discovered that hsa_circ_AKAP7 and other four circRNAs enriched in prostate cancer interfered with lipid metabolism pathway [ 116 ]. Likewise, circMAT2B was also found to regulate glycolysis in hepatocellular carcinoma [ 117 ].…”

The Role and Clinical Potentials of Circular RNAs in Prostate Cancer

“…For instance, Zhang et al (48) have identified 89 circRNAs which showed aberrant expression in PCa tissues, among them 32 circRNAs showed increased expression and remaining 57 demonstrated to be down-regulated. In further investigations, 5 prominently overexpressed circRNAs in comparison to their corresponding mRNAs in PCa tissues including hsa_circ_0006754, hsa_circ_0005848, hsa_circ_0006410, hsa_circ_0003970, and hsa_circ_AKAP7 were recognized.…”