Circular RNA profiling reveals circEXOC6B and circN4BP2L2 as novel prognostic biomarkers in epithelial ovarian cancer

Abstract

Circular RNAs (circRNAs) are regarded as a novel class of widespread endogenous non-coding RNAs, which may play important roles in tumorigenesis by regulating gene expression. Nevertheless, the characterization of circRNAs in epithelial ovarian cancer (EOC) remains largely unknown. This study aimed to investigate circRNA expression profiles in EOC. A total of 54 EOC specimens and 54 normal ovarian tissues (controls) were collected. circRNA-sequencing based circRNA expression profiles were identified in 4 EOC specimens and compared with 4 normal ovarian tissues. circRNA-sequencing data were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in the 54 EOC specimens and 54 normal ovarian tissues. The association between differentially expressed circRNAs and various clinicopathological features of EOC was determined using a non-parametric test. Univariate analysis was performed using the log-rank test. A total of 4,388 circRNAs (2,556 up-and 1,832 downregulated; fold change of ≥2 and P<0.05) were identified to be differentially expressed in the EOC specimens compared with the normal ovarian tissues. Of these, the levels of 6 circRNAs (circBNC2, circEXOC6B, circFAM13B, circ-N4BP2L2, circRHOBTB3 and circCELSR1) were confirmed by RT-qPCR. Our data further indicated that these 6 circRNAs were associated with various clinicopathological features of EOC. More importantly, we found that circEXOC6B and circ-N4BP2L2 may act as novel prognostic biomarkers in patients with EOC. On the whole, the results of this study indicate that differentially expressed circRNAs may participate in the pathogenesis of EOC and may thus have potential for use as novel diagnostic and prognostic biomarkers for EOC. Future experiments with larger sample sizes are required to verify the current findings and illuminate the regulatory mechanisms of action of circRNAs in the tumorigenesis of EOC.

<p>Circular RNA Circ_0025033 Promotes the Evolvement of Ovarian Cancer Through the Regulation of miR-330-5p/KLK4 Axis</p>

“…As a genre of novel ncRNA, circRNAs have become the research focus in various biological behaviors, including cell viability, apoptosis and metastasis of OC. 28,29 It is extremely significant to study how circRNAs generate their functions at the molecular level. In the current report, circ_0025033 was identified to regulate OC cellular processes through the miR-330-5p/KLK4 axis.…”

Comprehensive profiling of circular RNA expressions reveals potential diagnostic and prognostic biomarkers in multiple myeloma

“…With the rapid progression and wide application of high-throughput sequencing and microarray, the expression pattern of circRNAs in various human diseases are increasingly reported, and the dysregulated expressions of circRNAs are shown to contribute to the pathogenesis of various cancers [7,[9][10][11][14][15][16][17][18][19]. For instance, in hepatitis B-related HCC, 189 upregulated circRNAs and 37 downregulated circRNAs were found by circRNA microarray, and circRNA_100,338 is further validated to be associated with metastatic progression by acting as an endogenous sponge for miR-141-3p [7].…”

“…For instance, in hepatitis B-related HCC, 189 upregulated circRNAs and 37 downregulated circRNAs were found by circRNA microarray, and circRNA_100,338 is further validated to be associated with metastatic progression by acting as an endogenous sponge for miR-141-3p [7]. Another study identifies 2556 upregulated and 1832 downregulated cir-cRNAs in epithelial ovarian cancer tissues compared with normal ovarian tissues by microarray and bioinformatic analysis [11]. As for hematological malignancies, one previous study reveals the expression patterns of circRNAs in AML and exhibits 147 upregulated and 317 downregulated circRNAs in AML patients compared with healthy controls [10].…”

“…With the development of circRNA microarrays, our knowledge about circRNA expression patterns has been initially uncovered in various diseases. In cancer research, circRNA expression patterns have been studied in some solid tumors including breast cancer, esophageal squamous cell cancer, epithelial ovarian cancer, etc., and a number of circRNAs are disclosed to involve in the pathophysiological progression of these malignancies [8][9][10][11]. As for hematological malignancies, an extensive analysis of circRNA expression profiles reveals a total of 464 dysregulated circRNAs (147 upregulated and 317 downregulated) in acute myeloid leukemia (AML) patients compared with healthy controls, and among these circRNAs, circ_0004277 is validated to be positively associated with prognosis in AML patients [9].…”

Diagnostic value of circular RNAs in female reproductive system diseases: A PRISMA‑compliant meta‑analysis

“…Next, the enrolled studies only included data on those with preeclampsia, CSCC and BRCA. There are several other female reproductive system diseases that lack early diagnostic tools including repeated implantation failure and reproductive system malignancy such as ovarian cancer, the 5-year survival rate of which is only 30% as a vast majority of patients present with widespread metastasis (25,26). The lack of an effective molecular biomarker for diagnosing early stage ovarian cancer is a key contributor to its overall poor prognosis (27).…”