Department of Otolaryngology Head/Neck Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, P. R. China.
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20193788.
MiRNAlet-7a is associated with the tumorigenesis of laryngeal squamous cell carcinoma (LSCC). Our study was designed to infer whether let-7a targets high-mobility AT-hook 2 (HMGA2) and suppresses laryngeal carcinoma cell proliferation, invasion, and migration. The expression levels of let-7a and HMGA2 were measured in 30 LSCC clinical specimens by qRT-PCR and their correlation was analyzed. Cell model and mice xenograft model with or without let-7a overexpression were constructed to evaluate the effects of let-7a on LSCC. Moreover, luciferase assay was performed to reveal the interaction between let-7a and HMGA2, which was further verified in xenograft. Let-7a was significantly down-regulated and HMGA2 was up-regulated in LSCC tissues compared with normal tissues (P<0.05), both of which were significantly correlated with TNM stage and lymph node metastases of LSCC patients (P<0.05). We also observed a negative correlation between let-7a and HMGA2 expression in LSCC samples (r = -0.642, P<0.05). In vitro and in vivo experiments demonstrated that let-7a overexpression could inhibit cell proliferation and tumor growth of LSCC and simultaneously down-regulate the expression of HMGA2. Moreover, the regulation of HMGA2 by let-7a was also proved by luciferase assay. Our results revealed that let-7a promotes development and progression of LSCC through inhibiting the expression of HMGA2. Therefore, let-7a may thus be a potential diagnostic biomarker and therapeutic target for treating LSCC.
miRNAlet-7a 与喉鳞状细胞癌（LSCC）的发生有关。我们的研究旨在推断 let-7a 是否靶向高迁移率 AT 盒 2（HMGA2）并抑制喉癌细胞增殖、侵袭和迁移。通过 qRT-PCR 测量 30 例 LSCC 临床标本中 let-7a 和 HMGA2 的表达水平，并分析其相关性。构建了具有或不具有 let-7a 过表达的细胞模型和小鼠异种移植模型，以评估 let-7a 对 LSCC 的影响。此外，进行了荧光素酶测定以揭示 let-7a 与 HMGA2 之间的相互作用，并且在异种移植中进一步验证了该相互作用。与正常组织相比，LSCC 组织中 let-7a 显著下调，HMGA2 上调（P<0.05），并且与 LSCC 患者的 TNM 分期和淋巴结转移均显著相关（P<0.05）。我们还观察到 LSCC 样本中 let-7a 和 HMGA2 表达之间存在负相关（r = -0.642，P<0.05）。体外和体内实验表明，let-7a 过表达可抑制 LSCC 细胞增殖和肿瘤生长，同时下调 HMGA2 的表达。此外，荧光素酶测定还证明了 let-7a 对 HMGA2 的调节作用。我们的研究结果表明，let-7a 通过抑制 HMGA2 的表达促进 LSCC 的发展和进展。因此，let-7a 可能是治疗 LSCC 的潜在诊断生物标志物和治疗靶标。
