Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, PR. China.
Bioengineered. 2022 Mar;13(3):6929-6941. doi: 10.1080/21655979.2022.2034703.
Emerging evidence has revealed that aberrantly expressed circular RNAs (circRNAs) play vital roles in tumorigenesis and progression of diverse human malignancies. CircZNF609 was found to be involved in hepatocellular carcinoma, but the role and underlying mechanism of circZNF609 in laryngeal squamous cell carcinoma (LSCC) remain unclear. This study aimed to explore the molecular mechanism of circZNF609 in LSCC. qRT-qPCR was performed to detect the expression of circZNF609 and microRNA-134-5p (miR-134-5p) in LSCC. Colony formation assay, CCK-8 assay, BrdU incorporation assay, clone formation assay, transwell invasion assay and Western blot analysis were performed to evaluate LSCC cell proliferation, as well as the expression of proliferating cell nuclear antigen (PCNA) and MMP-2. Luciferase reporter assay, target gene prediction and screening were used to validate downstream target genes of circZNF609 and miR-134-5p. EGFR expression was detected by Western blot analysis and RT-qPCR. Nude mice were used to detect tumor changes. CircZNF609 was upregulated in LSCC and associated with poor survival of LSCC patients. Knockdown of circZNF609 inhibited LSCC proliferation, invasion and the expression of PCNA and matrix matalloproteinases-2 (MMP-2). CircZNF609 can regulate miR-134-5p to upregulate epidermal growth factor receptor (EGFR). In addition, knockdown of EGFR or overexpression of miR-134-5p could reverse the tumor-promoting effects of circZNF609 in LSCC. In LSCC tissues, circZNF609 was negatively correlated with miR-134-5p and positively correlated with EGFR. CircZNF609 promotes the progression of LSCC via the miR-134-5p/EGFR axis, which might be the therapeutic target of LSCC.
越来越多的证据表明,异常表达的环状 RNA(circRNA)在多种人类恶性肿瘤的发生和发展中起着至关重要的作用。CircZNF609 被发现参与肝细胞癌,但 circZNF609 在喉鳞状细胞癌(LSCC)中的作用和潜在机制尚不清楚。本研究旨在探讨 circZNF609 在 LSCC 中的分子机制。qRT-qPCR 用于检测 LSCC 中 circZNF609 和 microRNA-134-5p(miR-134-5p)的表达。集落形成实验、CCK-8 实验、BrdU 掺入实验、克隆形成实验、Transwell 侵袭实验和 Western blot 分析用于评估 LSCC 细胞的增殖以及增殖细胞核抗原(PCNA)和 MMP-2 的表达。荧光素酶报告实验、靶基因预测和筛选用于验证 circZNF609 和 miR-134-5p 的下游靶基因。Western blot 分析和 RT-qPCR 用于检测 EGFR 的表达。裸鼠用于检测肿瘤变化。CircZNF609 在 LSCC 中上调,并与 LSCC 患者的不良生存相关。circZNF609 的敲低抑制了 LSCC 的增殖、侵袭以及 PCNA 和基质金属蛋白酶-2(MMP-2)的表达。CircZNF609 可以调节 miR-134-5p 以上调表皮生长因子受体(EGFR)。此外,EGFR 的敲低或 miR-134-5p 的过表达可以逆转 circZNF609 在 LSCC 中的促肿瘤作用。在 LSCC 组织中,circZNF609 与 miR-134-5p 呈负相关,与 EGFR 呈正相关。CircZNF609 通过 miR-134-5p/EGFR 轴促进 LSCC 的进展,这可能是 LSCC 的治疗靶点。