Molecular mechanism of targeted inhibition of HMGA2 via miRNAlet-7a in proliferation and metastasis of laryngeal squamous cell carcinoma. Issue 6 (3rd June 2020)

• Record Type: Journal Article
• Authors: Ma, Li-Juan; Wu, Jun; Zhou, En; Yin, Juan; Xiao, Xu-Ping
• Is Part Of: Bioscience reports. Volume 40:Issue 6(2020)
• Publication Date: 2020-06-03
• Subjects: cell apoptosis -- cell proliferation -- HMGA2 -- laryngeal squamous cell carcinoma -- MiRNAlet-7a; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20193788
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract: 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.