Xue Feifei, Feng Hongjie, Wang Tianxiao, Feng Guanying, Ni Nan, Wang Ruixia, Yuan Hua
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Oral Dis. 2023 Oct;29(7):2677-2688. doi: 10.1111/odi.14399. Epub 2022 Oct 20.
Circular RNAs (CircRNAs) are involved in various tumors. However, their role in head and neck squamous cell carcinoma (HNSCC) is unknown. CircRNA sequencing data showed that hsa_circ_0000264 is significantly upregulated in HNSCC tissues. In this study, we aimed to investigate the role of hsa_circ_0000264 in HNSCC and elucidate its underlying regulation mechanism.
RNase R treatment was performed to confirm the loop structure of hsa_circ_0000264. Fluorescence in situ hybridization was performed to show the subcellular localization of hsa_circ_0000264. We then performed wound healing assay, Transwell assay, Western blot, and in vivo experiments to determine the effect of alterations in hsa_circ_0000264 expression. We performed RNA pull-down and dual luciferase reporter assay to identify and confirm the binding sites in RNAs.
hsa_circ_0000264 was upregulated in HNSCC tissues and cells, and its loop structure was confirmed. Knockdown of hsa_circ_0000264 inhibited the migration, invasion, and epithelial-to-mesenchymal transition of HNSCC cells in vivo and in vitro. Mechanistically, hsa_circ_000026 upregulation can upregulate the expression of high mobility group AT-hook 2 (HMGA2) by sponging hsa-let-7b-5p, which in turn promotes HNSCC progression.
Our results showed that hsa_circ_0000264 promotes HNSCC progression via the hsa-let-7b-5p/HMGA2 axis, and hsa_circ_0000264 can serve as a potential target for HNSCC treatment.
环状RNA（CircRNAs）参与多种肿瘤的发生发展。然而，它们在头颈部鳞状细胞癌（HNSCC）中的作用尚不清楚。环状RNA测序数据显示，hsa_circ_0000264在HNSCC组织中显著上调。在本研究中，我们旨在探讨hsa_circ_0000264在HNSCC中的作用，并阐明其潜在的调控机制。
进行核糖核酸酶R处理以确认hsa_circ_0000264的环状结构。进行荧光原位杂交以显示hsa_circ_0000264的亚细胞定位。然后，我们进行了伤口愈合试验、Transwell试验、蛋白质免疫印迹法及体内实验，以确定hsa_circ_0000264表达改变的影响。我们进行了RNA下拉试验和双荧光素酶报告基因试验，以鉴定和确认RNA中的结合位点。
hsa_circ_0000264在HNSCC组织和细胞中上调，其环状结构得到确认。敲低hsa_circ_0000264可在体内外抑制HNSCC细胞的迁移、侵袭及上皮-间质转化。机制上，hsa_circ_000026上调可通过海绵吸附hsa-let-7b-5p上调高迁移率族AT钩蛋白2（HMGA2）的表达，进而促进HNSCC进展。
我们的结果表明，hsa_circ_0000264通过hsa-let-7b-5p/HMGA2轴促进HNSCC进展，hsa_circ_0000264可作为HNSCC治疗的潜在靶点。
