Circular RNA profiling reveals a potential role of hsa_circ_IPCEF1 in papillary thyroid carcinoma

Abstract

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that are expressed across species and are implicated in cellular biological processes, displaying dysregulated expression in various tumorigeneses. Therefore, circRNA deregulation could be a crucial event in thyroid carcinoma. The present study identified circRNA signatures in several patients with papillary thyroid carcinoma (PTC) to complement the understanding of PTC pathogenesis. Using microarray technology, the circRNA profiles in three pairs of PTC tumors and matching adjacent normal tissues were screened. Differentially expressed circRNAs were further validated by reverse transcription-quantitative PCR in whole blood from 57 pairs of subjects. Bioinformatics data analyses including miRNA response element prediction, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway, competing endogenous RNA and KEGG Orthology-Based Annotation System analyses were performed to predict circRNA associations with cancer-related putative downstream miRNAs and target genes. Receiver operating characteristic curves and the area under the curve (AUC) values were acquired to assess the performance of validated circRNAs in predicting potential associations with PTC. In total, 158 dysregulated circRNAs were identified in PTC tumors relative to adjacent normal tissues. Notably, one downregulated circRNA (hsa_circ_IPCEF1) showed the preferable predictive power (AUC=0.8010, P<0.0001) and interactions with four cancer-related genes (CASR, CDC25B, NFκB1 and SHOC2). From these analyses, one PTC-related miRNA (hsa-miR-3619-5p) was identified as a potential target for hsa_circ_IPCEF1 sponging, indicating the hsa_circ_ IPCEF1/hsa-miR-3619-5p axis in pathogenesis.

Function and Clinical Significance of Circular RNAs in Thyroid Cancer

“…In contrast, circ-ITCH is downregulated in PTC tissues and cell lines, and its expression levels are significantly associated with LNM (p = 0.020), clinical stage (p = 0.022) (Wang M. et al, 2018). Similarly, hsa_circ_IPCEF1 is significantly decreased in both PTC tissues and blood, and its levels were positively correlated with LNM (p < 0.001) (Guo et al, 2021). Most studies have reported that there is no relationship between circRNA levels and gender in TC.…”

“…RNA-seq, circRNA-specific microarrays and bioinformatics analyses are the most commonly used methods for genomewide profiling of circRNAs, and thousands of circRNAs have been identified in tissues, cells, exosomes, and blood of patients with TC (Table 1) (Peng et al, 2017;Hou et al, 2018;Lan et al, 2018b;Ren et al, 2018;Yang et al, 2019;Chu et al, 2020b;Liu et al, 2020b;Liu Q et al, 2020;Long et al, 2020;Sun J. W. et al, 2020;Yang W. et al, 2020;Yang Y. et al, 2020;Yu et al, 2020;Chu et al, 2021;Guo et al, 2021;Li et al, 2021b;Lv et al, 2021;Qiu et al, 2021;Zhang et al, 2022). Hundreds of differentially expressed circRNAs (DECs) were identified between the tumour and non-tumour groups.…”

“…Compared with normal controls, circRNAs present significantly differential expression profiles in TC tissues and blood from patients with TC; thus, they are regarded as promising and ideal candidates for the diagnosis of TC owing to their abnormal expression and high specificity (Table 2; Figure 4) (Jin et al, 2018;Lan et al 2018a;Ren et al 2018;Wang et al 2018b;Wei et al 2018;Cai et al 2019;Yao et al 2019;Wang et al 2019a;Fan et al 2020;Han et al 2020a;Hu et al 2020b;Liu et al 2020b;Sun et al 2020b;Wang et al 2020b;Wu et al 2020a;Xue et al 2020;Ye et al, 2020;Yu et al, 2020;Zhang et al 2020b;Chu et al, 2021;Ding et al 2021a;Ding et al 2021b;Du et al 2021;Guo et al 2021;Li et al 2021a;Li et al 2021b;Li et al 2021d;Lin et al 2021;Liu et al 2021b;Luo et al, 2021;Ma and Kan, 2021;Qi et al, 2021b;Xiong et al, 2021b;Zeng et al, 2021;Zhang et al 2021c;Zhang et al 2021d;Zheng et al 2021a;Zhu et al, 2021;…”

“…Finally, defining a precise prognosis for TC patients is essential for physicians to formulate the best treatment decisions. To further analyse the prognostic value of circRNAs in TC, we collected information from studies reporting survival information and evaluated the associations between circRNA expression levels and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) (Table 2) (Jin et al, 2018;Lan et al 2018a;Ren et al 2018;Wang et al 2018b;Wei et al 2018;Cai et al 2019;Yao et al 2019;Wang et al 2019a;Fan et al 2020;Han et al 2020a;Hu et al 2020b;Liu et al 2020b;Shi et al 2020;Sun et al 2020b;Wang et al 2020b;Wu et al 2020a;Xue et al 2020;Ye et al, 2020;Yu et al, 2020;Chu et al, 2021;Ding et al 2021a;Ding et al 2021b;Du et al 2021;Guo et al 2021;Li et al 2021a;Li et al 2021b;Li et al 2021d;Lin et al 2021;Liu et al 2021b;Luo et al, 2021;Ma and Kan, 2021;Qi et al, 2021b;Xiong et al, 2021b;Zeng et al, 2021;Zhang et al 2021c;Zhang et al 2021d;Zheng et al 2021a;…”

Development of a joint diagnostic model of thyroid papillary carcinoma with artificial neural network and random forest

“…IPCEF1 was viewed as a significant biomarker for PTC. Moreover, a study showed that the hsa_circ_IPCEF1/hsa-miR-3619-5p axis was associated with the mechanism of PTC, which offers a new idea for further diagnosis and treatment of PTC (Guo et al, 2021). Several researchers revealed noticeable differences in Trefoil factor 3 (TFF3) between benign thyroid nodules and thyroid malignancy (Krause et al, 2008;Karger et al, 2012).…”