Comprehensive analysis of the whole coding and non-coding RNA transcriptome expression profiles and construction of the circRNA–lncRNA co-regulated ceRNA network in laryngeal squamous cell carcinoma

Rui Zhao, Feng-Qing Li, Lin-Li Tian, De-Si Shang, Yan Guo, Jia-Rui Zhang, Ming Liu

Recently, accumulating evidence has demonstrated that non-coding RNAs (ncRNAs) play a vital role in oncogenicity. Nevertheless, the regulatory mechanisms and functions remain poorly understood, especially for lncRNAs and circRNAs. In this study, we simultaneously detected, for the first time, the expression profiles of the whole transcriptome, including miRNA, circRNA and lncRNA + mRNA, in five pairs of laryngeal squamous cell carcinoma (LSCC) and matched non-carcinoma tissues by microarrays. Five miRNAs, four circRNAs, three lncRNAs and five mRNAs that were dysregulated were selected to confirm the verification of the microarray data by quantitative real-time PCR (qRT-PCR) in 20 pairs of LSCC samples. We constructed LSCC-related competing endogenous RNA (ceRNA) networks of lncRNAs and circRNAs (circRNA or lncRNA-miRNA-mRNA) respectively. Functional annotation revealed the lncRNA-mediated ceRNA network were enriched for genes involved in the tumor-associated pathways. Hsa_circ_0033988 with the highest degree in the circRNA-mediated ceRNA network was associated with fatty acid degradation, which was responsible for the depletion of fat in tumor-associated cachexia. Finally, to clarify the ncRNA co-regulation mechanism, we constructed a circRNA-lncRNA co-regulated network by integrating the above two networks and identified 9 modules for further study. A subnetwork of module 2 with the most dysregulated microRNAs was extracted to establish the ncRNA-involved TGF-β-associated pathway. In conclusion, our findings provide a high-throughput microarray data of the coding and non-coding RNAs and establish the foundation for further functional research on the ceRNA regulatory mechanism of non-coding RNAs in LSCC.