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.
Highlights
Laryngeal squamous cell carcinoma (LSCC) is a common type of head and neck cancer, which accounts for 5.7–7.6% of all malignant tumors [1]
We showed that let-7a was down-regulated and high-mobility group A2 (HMGA2) was up-regulated in LSCC tissues compared with normal tissues, which were both associated with clinical TNM stage and lymph node metastases
For preliminarily exploring the role of let-7a and HMGA2 in LSCC, the expression levels were detected 30 freshly frozen LSCC tissues compared with paracarcinoma normal tissues
Summary
Laryngeal squamous cell carcinoma (LSCC) is a common type of head and neck cancer, which accounts for 5.7–7.6% of all malignant tumors [1]. The HMGA2 gene is located on chromosome 12q13–15 and encodes HMGA2 protein containing 109 amino acids. It has been recognized as a new oncogene that may contribute to tumorigenesis, invasiveness, and metastasis. Studies showed that its transcripts were hardly detected in late stages of embryonic development or in completely differentiated mature cells and tissues. It was highly expressed in many malignant and benign tumors, such as nasopharyngeal carcinoma [3], pancreatic [4], gastric [5], colon [6], and ovarian cancers
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