Liu Xiaoyan, Zeng Lili, Wang Wenlong, Li Zhipeng, Zhou Siyuan, Wang Fang, Wang Yue, Du Jing, Ma Xiangrui
Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China.
School of Stomatology, Binzhou Medical University, Yantai, Shandong 264000, P.R. China.
Oncol Lett. 2023 Aug 22;26(4):435. doi: 10.3892/ol.2023.14022. eCollection 2023 Oct.
Circular RNAs (circRNAs) are molecular sponges that are involved in regulation of multiple types of cancer. The present study aimed to screen and explore the key circRNA/microRNA (miRNA or miR)/mRNA interactions in head and neck squamous cell carcinoma (HNSCC) using bioinformatics. A total of six pairs of cancerous and adjacent healthy tissue were obtained from patients with HNSCC and genome-wide transcriptional sequencing was performed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed genes (DEGs). Moreover, expression levels of DEGs were verified in HNSCC cells and tissues using reverse transcription-quantitative (RT-q)PCR. A molecular regulatory network consisting of three circRNAs, seven miRNAs and seven mRNAs was constructed, resulting in identification of two signaling axes, hsa_circ_0035431/hsa-miR-940/fucosyltransferase 6 (FUT6) and hsa_circ_0035431/hsa-miR-940/cingulin-like 1 (CGNL1). FUT6 and CGNL1 were downregulated in HNSCC compared with adjacent healthy tissue and the expression levels of these genes were associated with tumor stage. Low FUT6 and CGNL1 expression levels were associated with lower overall survival rate and progression-free intervals in HNSCC. RT-qPCR demonstrated that hsa_circ_0035431, FUT6 and CGNL1 were downregulated in HNSCC cells and tissue and hsa-miR-940 was upregulated. Notably, these results were consistent with those obtained using high-throughput sequencing. In conclusion, hsa_circ_0035431 may participate in regulation of FUT6 and CGNL1 expression by sponging hsa-miR-940, thus, impacting the occurrence, development and prognosis of HNSCC.
环状RNA（circRNAs）是参与多种癌症调控的分子海绵。本研究旨在利用生物信息学筛选并探索头颈部鳞状细胞癌（HNSCC）中关键的circRNA/微小RNA（miRNA或miR）/信使核糖核酸（mRNA）相互作用。从HNSCC患者中获取了总共6对癌组织和相邻的健康组织，并进行了全基因组转录测序。对差异表达基因（DEGs）进行了基因本体论和京都基因与基因组百科全书通路富集分析。此外，使用逆转录定量（RT-q）PCR在HNSCC细胞和组织中验证了DEGs的表达水平。构建了一个由3个circRNAs、7个miRNAs和7个mRNAs组成的分子调控网络，从而鉴定出两条信号轴，即hsa_circ_0035431/hsa-miR-940/岩藻糖基转移酶6（FUT6）和hsa_circ_0035431/hsa-miR-940/带状肌动蛋白样蛋白1（CGNL1）。与相邻健康组织相比，FUT6和CGNL1在HNSCC中表达下调，并且这些基因的表达水平与肿瘤分期相关。FUT6和CGNL1低表达水平与HNSCC患者较低的总生存率和无进展生存期相关。RT-qPCR表明，hsa_circ_0035431、FUT6和CGNL1在HNSCC细胞和组织中表达下调，而hsa-miR-940表达上调。值得注意的是，这些结果与高通量测序获得的结果一致。总之，hsa_circ_0035431可能通过吸附hsa-miR-940参与FUT6和CGNL1表达的调控，从而影响HNSCC的发生、发展和预后。
