Analysis of the circular RNA transcriptome in the grade 3 endometrial cancer

Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have shown large capabilities in gene regulation. Patients with the grade 3 endometrial cancer (EC) have a generally poor prognosis, and the specific role of circRNAs in the grade 3 EC remains unclear. This study aims to investigate the roles of circRNAs in the grade 3 EC.

In the current study, we screened the expression profiles of circRNAs taken from two women with the grade 3 EC and adjacent non-cancerous endometrial tissue using circRNAs sequencing. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) of six dysregulated circRNAs was performed to validate the sequencing results. Bioinformatic analyses, including the negative correlation network analyses of circRNAs-microRNAs (miRNAs)-messenger RNAs (mRNAs) and the Cytoscape, were used to delineate the interaction of circRNAs/miRNAs of the entire network.

Data of circRNA sequencing showed a significant change in 75,928 unique circRNAs (P<0.05). The upregulated hsa_circ_0039569 and hsa_circ_0001610 and downregulated hsa_circ_0000437, hsa_circ_0001776, and hsa_circ_0009043 were validated by qRT-PCR analysis. Using bioinformatical methods, we found that hsa_circ_0039569 has the MRE of hsa-miR-542-3p and hsa-let-7c-5p. Hsa-miR-542-3p and hsa-let-7c-5p were downregulated in the grade 3 EC validated by qRT-PCR analysis. In the clinicopathological parameters, the expression level of hsa_circ_0039569 was significantly correlated with tumor differentiation (P=0.001).

This is the first study demonstrated that there were a lot of differences between the tissue of the grade 3 EC and adjacent non-cancerous endometrial in circRNA expression and may offer novel molecular candidates for diagnosis and clinical treatment of the grade 3 EC.