Tian Kaisai, Zheng Liying, Yuan Tailei, Chen Xiaoping, Chen Qun, Xue Xiaocheng, Huang Shuixian, He Weining, Jin Mingming, Zhang Yi
Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai, 200135, China.
Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, China.
Cancer Cell Int. 2024 Mar 1;24(1):91. doi: 10.1186/s12935-024-03256-x.
Circular RNAs (circRNAs) belong to a class of covalently closed single stranded RNAs that have been implicated in cancer progression. Former investigations showed that hsa-circ-0013561 is abnormally expressed in head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of hsa-circ-0013561 during the progress of HNSCC still unclear.
Present study applied FISH and qRT-PCR to examine hsa-circ-0013561 expression in HNSCC cells and tissue samples. Dual-luciferase reporter assay was employed to identify downstream targets of hsa-circ-0013561. Transwell migration, 5-ethynyl-2'-deoxyuridine incorporation, CCK8 and colony formation assays were utilized to test cell migration and proliferation. A mouse tumor xenograft model was utilized to determine the hsa-circ-0013561 roles in HNSCC progression and metastasis in vivo.
We found that hsa-circ-0013561 was upregulated in HNSCC tissue samples. hsa-circ-0013561 downregulation inhibited HNSCC cell proliferation and migration to promote apoptosis and G1 cell cycle arrest. The dual-luciferase reporter assay revealed that miR-7-5p and PDK3 are hsa-circ-0013561 downstream targets. PDK3 overexpression or miR-7-5p suppression reversed the hsa-circ-0013561-induced silencing effects on HNSCC cell proliferation and migration. PDK3 overexpression reversed miR-7-5p-induced effects on HNSCC cell proliferation and migration.
The findings suggest that hsa-circ-0013561 downregulation inhibits HNSCC metastasis and progression through PDK3 expression and miR-7-5p binding modulation.
环状RNA（circRNAs）属于一类共价闭合的单链RNA，与癌症进展有关。先前的研究表明，hsa-circ-0013561在头颈部鳞状细胞癌（HNSCC）中异常表达。然而，hsa-circ-0013561在HNSCC进展过程中的作用仍不清楚。
本研究应用荧光原位杂交（FISH）和定量逆转录聚合酶链反应（qRT-PCR）检测hsa-circ-0013561在HNSCC细胞和组织样本中的表达。采用双荧光素酶报告基因检测法鉴定hsa-circ-0013561的下游靶点。利用Transwell迁移、5-乙炔基-2'-脱氧尿苷掺入、CCK8和集落形成试验检测细胞迁移和增殖。利用小鼠肿瘤异种移植模型确定hsa-circ-0013561在体内HNSCC进展和转移中的作用。
我们发现hsa-circ-0013561在HNSCC组织样本中上调。hsa-circ-0013561的下调抑制了HNSCC细胞的增殖和迁移，促进了细胞凋亡和G1期细胞周期阻滞。双荧光素酶报告基因检测显示，miR-7-5p和PDK3是hsa-circ-0013561的下游靶点。PDK3的过表达或miR-7-5p的抑制逆转了hsa-circ-0013561对HNSCC细胞增殖和迁移的沉默作用。PDK3的过表达逆转了miR-7-5p对HNSCC细胞增殖和迁移的影响。
研究结果表明，hsa-circ-0013561的下调通过调节PDK3表达和miR-7-5p结合抑制HNSCC转移和进展。
