RNA-Seq profiling of circular RNAs in human laryngeal squamous cell carcinomas

Abstract

Abnormal expression of non-coding circular RNAs (circRNAs) have been reported in many types of tumors. circRNA have been suggested to be an ideal candidate biomarker for diagnostic and therapeutic implications in cancers. The aim of this study was to assess the circRNA expression profile of laryngeal squamous cell carcinomas (LSCC). The biopsy samples from patients with LSCC were obtained intra-operatively. The circRNA expression was performed using secondary sequencing. Among 10 patients with LSCC, 2 were well differentiated, 3 were moderately differentiated and 5 were adjunctive samples with normal and LSCC tissues. A total of 21,444 distinct circRNA candidates were detected. Among them, we defined the statistical criteria for selecting aberrant-expressed circRNA using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. A total of 29 circRNA were upregulated and 19 circRNA were downregulated significantly in the LSCC tissues. The intersection of these dysregulated circRNAs of normal-well differentiated set and normal-moderately differentiated set was then assessed to narrow the upregulated and downregulated circRNAs down to 18 and 5 respectively. Furthermore, an association of the circRNA-miRNA-mRNA was investigated, showing that 20 dysregulated circRNA successfully predicted an interaction with several cancer-related miRNAs. Finally, a further KEGG analysis showed that PPAR, Axon guidance, Wnt and Cell cycle signaling pathway were key putative pathways in the process of LSCC. hsa_circ:chr20:31876585–31,897,648 was found to be able to differentiate most of LSCC from the matching normal tissues. This observational study demonstrated dysregulation of circRNA in LSCC, which may have an impact on development of potential biomarkers in this disease. Validation of down-regulation of hsa_circ:chr20:31876585–31,897,648 in LSCC compared to each adjunctive tissue by Q-RT-PCR, indicating that hsa_circ:chr20:31876585–31,897,648 may be a novel promising tumor suppresser in LSCC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0833-x) contains supplementary material, which is available to authorized users.

Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis

“…Studies have shown that circRNA has important regulatory effects in a variety of biological processes, especially in the occurrence, development, and metastasis of various malignant tumors [22][23][24]. circRNA expression profiling revealed a series of differentially expressed cir-cRNAs in LSCC tissues [25,26], suggesting that cir-cRNA may have important roles in the occurrence and progression of LSCC. In this study, we performed largescale RNA sequencing of LSCC and matched ANM tissues, and established the circRNA, miRNA, and mRNA expression profiles of LSCC tissues.…”

Circular RNAs and their roles in head and neck cancers

“…After integrating the comparison results of "moderately differentiated LSCC vs ANTs" and "well differentiated LSCC vs ANTs", there were 18 consistently downregulated circRNAs and 5 upregulated circRNAs in Table 4 The potential function and the mechanism of the dysregulated circRNAs in HNCs Note: HNSCC head and neck squamous cell carcinoma, OSCC oral squamous cell carcinoma, LSCC laryngeal squamous cell carcinoma, HSCC hypopharyngeal squamous cell carcinoma, NPC nasopharyngeal carcinoma, "-" means not investigated in the paper, "*" means based on bioinformatics analysis but not validated experimentally LSCC. Moreover, the downregulation of hsa_circ: chr20:31876585-31,897,648 with most predicted target miRNAs was validated by qRT-PCR, demonstrating its potential as a diagnostic biomarker for LSCC [171]. However, the results need to be verified in a larger group because the sample size of this study was small, and the dysregulated circRNAs with the largest change-fold were not discussed.…”

“…Recently, NGS was conducted to investigate the cir-cRNA profiles in LSCC, which could account for the cir-cRNAs that are not present on the microarray [171]. Three moderately differentiated LSCC samples, two well-differentiated LSCC samples and five corresponding ANT samples were included.…”

Comparison of dysregulated long noncoding RNAs in lung adenocarcinoma and spinal metastasis: A genome-wide analysis

“…The significant function of lncRNAs has been widely acknowledged, with recent evidence confirming that lncRNAs play an important role in carcinogenesis and tumor metastasis [23,24]. Up-and downregulated lncRNAs may be important molecular markers for cancer diagnosis, therapy and tumor metastasis [25][26][27].…”