PMID- 32432318 OWN - NLM STAT- MEDLINE DCOM- 20210330 LR - 20240328 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 40 IP - 6 DP - 2020 Jun 26 TI - Molecular mechanism of targeted inhibition of HMGA2 via miRNAlet-7a in proliferation and metastasis of laryngeal squamous cell carcinoma. LID - 10.1042/BSR20193788 [doi] LID - BSR20193788 AB - 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. CI - (c) 2020 The Author(s). FAU - Ma, Li-Juan AU - Ma LJ AD - Department of Otolaryngology Head/Neck Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, P. R. China. FAU - Wu, Jun AU - Wu J AD - Department of Otolaryngology Head/Neck Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, P. R. China. FAU - Zhou, En AU - Zhou E AD - Department of Otolaryngology Head/Neck Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, P. R. China. FAU - Yin, Juan AU - Yin J AD - Department of Otolaryngology Head/Neck Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, P. R. China. FAU - Xiao, Xu-Ping AU - Xiao XP AD - Department of Otolaryngology Head/Neck Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (Biomarkers, Tumor) RN - 0 (HMGA2 Protein) RN - 0 (HMGA2 protein, human) RN - 0 (MicroRNAs) RN - 0 (mirnlet7 microRNA, human) SB - IM MH - Animals MH - Biomarkers, Tumor/genetics/*metabolism MH - Cell Line, Tumor MH - *Cell Movement MH - *Cell Proliferation MH - Female MH - Gene Expression Regulation, Neoplastic MH - HMGA2 Protein/genetics/*metabolism MH - Humans MH - Laryngeal Neoplasms/genetics/*metabolism/pathology MH - Lymphatic Metastasis MH - Male MH - Mice, Inbred BALB C MH - MicroRNAs/genetics/*metabolism MH - Middle Aged MH - Neoplasm Staging MH - Signal Transduction MH - Squamous Cell Carcinoma of Head and Neck/genetics/*metabolism/secondary MH - Tumor Burden PMC - PMC7269914 OTO - NOTNLM OT - HMGA2 OT - MiRNAlet-7a OT - cell apoptosis OT - cell proliferation OT - laryngeal squamous cell carcinoma COIS- The authors declare that there are no competing interests associated with the manuscript. EDAT- 2020/05/21 06:00 MHDA- 2021/03/31 06:00 PMCR- 2020/06/03 CRDT- 2020/05/21 06:00 PHST- 2019/10/30 00:00 [received] PHST- 2020/05/14 00:00 [revised] PHST- 2020/05/15 00:00 [accepted] PHST- 2020/05/21 06:00 [pubmed] PHST- 2021/03/31 06:00 [medline] PHST- 2020/05/21 06:00 [entrez] PHST- 2020/06/03 00:00 [pmc-release] AID - 224886 [pii] AID - BSR20193788 [pii] AID - 10.1042/BSR20193788 [doi] PST - ppublish SO - Biosci Rep. 2020 Jun 26;40(6):BSR20193788. doi: 10.1042/BSR20193788.