Guo Yang, Huang Qiang, Zheng Juan, Hsueh Chi-Yao, Yuan Xiaohui, Heng Yu, Zhou Liang
Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, People's Republic of China.
Onco Targets Ther. 2020 Jun 17;13:5709-5719. doi: 10.2147/OTT.S231076. eCollection 2020.
Dysregulated circular RNAs (circRNAs) have been shown to play important roles in various cancers, and could serve as diagnostic biomarkers. However, research focusing on the roles of the circRNAs in laryngeal squamous cell carcinoma (LSCC) is limited. This research aimed to explore the expressions of hsa_circ_0036722 in LSCCs and its diagnostic significance.
The expression levels of the circular RNA, hsa_circ_0036722, and its parental gene, RHCG, in 41 pairs of LSCC tissues and paired adjacent normal tissues were validated with quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic values of hsa_circ_0036722 alone and combined with RHCG in LSCC were evaluated using receiver operating characteristic (ROC) curves. Bioinformatics analysis predicted likely cross-talk between hsa_circ_0036722 and RHCG. Then, qRT-PCR and luciferase reporter assay were used to examine the effect of hsa_circ_0036722 on miR-1248 and miR‑1248 on RHCG expression. CCK-8 assays were conducted to investigate their effects on LSCC cell line.
Hsa_circ_0036722 and RHCG were downregulated in LSCC tissues ( < 0.0001). The expression level of hsa_circ_0036722 was significantly correlated with the differentiation level of LSCC ( = 0.018). The area under the ROC curve of hsa_circ_0036722 was 0.838, which reached 0.859 when hsa_circ_0036722 was combined with RHCG as a biomarker. Mechanistically, hsa_circ_0036722 could directly sponge miR-1248 to antagonize its inhibitory effect on RHCG. And downregulation of hsa_circ_0036722 could promote the proliferation of LSCC cell line through upregulating miR-1248.
Our results indicated that hsa_circ_0036722 was downregulated in LSCC, which regulate the function of RHCG in LSCC via inhibiting miR-1248, and it could serve as a potential diagnostic marker for LSCC.
失调的环状RNA(circRNAs)已被证明在多种癌症中发挥重要作用,并可作为诊断生物标志物。然而,针对circRNAs在喉鳞状细胞癌(LSCC)中作用的研究有限。本研究旨在探讨hsa_circ_0036722在LSCC中的表达及其诊断意义。
采用定量实时聚合酶链反应(qRT-PCR)验证41对LSCC组织及配对的癌旁正常组织中环状RNA hsa_circ_0036722及其亲本基因RHCG的表达水平。使用受试者工作特征(ROC)曲线评估hsa_circ_0036722单独及与RHCG联合用于LSCC诊断的价值。生物信息学分析预测了hsa_circ_0036722与RHCG之间可能的相互作用。然后,采用qRT-PCR和荧光素酶报告基因检测法检测hsa_circ_0036722对miR-1248的影响以及miR-1248对RHCG表达的影响。进行CCK-8检测以研究它们对LSCC细胞系的作用。
hsa_circ_0036722和RHCG在LSCC组织中表达下调(<0.0001)。hsa_circ_0036722的表达水平与LSCC的分化程度显著相关(=0.018)。hsa_circ_0036722的ROC曲线下面积为0.838,当hsa_circ_0036722与RHCG联合作为生物标志物时,该面积达到0.859。机制上,hsa_circ_0036722可直接吸附miR-1248以拮抗其对RHCG的抑制作用。hsa_circ_0036722的下调可通过上调miR-1248促进LSCC细胞系的增殖。
我们的结果表明,hsa_circ_0036722在LSCC中表达下调,其通过抑制miR-1248调节RHCG在LSCC中的功能,并且它可作为LSCC的潜在诊断标志物。