PMID- 29843929 OWN - NLM STAT- MEDLINE DCOM- 20190610 LR - 20190619 IS - 1879-1476 (Electronic) IS - 0385-8146 (Linking) VI - 46 IP - 1 DP - 2019 Feb TI - MicroRNA-4497 functions as a tumor suppressor in laryngeal squamous cell carcinoma via negatively modulation the GBX2. PG - 106-113 LID - S0385-8146(18)30168-8 [pii] LID - 10.1016/j.anl.2018.05.005 [doi] AB - OBJECTIVE: MicroRNAs (miRNAs) are aberrantly expressed in various tumors and play a critical role in the progression and development of tumors. However, there is little information about the role of miR-4497 in laryngeal squamous cell carcinoma (LSCC). The aim of this study is to investigate the role of miR-4497 in LSCC. METHODS: MiR-4497 expression in tumor tissues and adjacent normal tissues was measured by RT-PCR. The effects of miR-4497 on cell viability and apoptosis were evaluated by the MTT assay, Flow cytometry and caspase-3 activity assay. Western blot analysis was used to measure the expression of various proteins. Bioinformatic analysis and luciferase reporter assay were applied to investigate the relationship between miR-4497 and GBX2. RESULTS: We found that miR-4497 expression was downregulated in LSCC tumor tissues and cell lines compared to the normal counterparts. Overexpression of miR-4497 inhibits the proliferation and induces apoptosis of LSCC cells accompanied by the down-regulation of anti-apoptotic Bcl-2 proteins. Mechanisms investigation revealed that GBX2 is a direct target of miR-4497. miR-4497 expression was inversely correlated with GBX2 expression in LSCC tissues. Moreover, overexpression of miR-4497 leads to the activation of ERK, JNK but not p38. Inhibition of ERK by specific inhibitor SCH772984 could interfere the apoptosis induced by overexpression of miR-4497. CONCLUSION: Therefore, our results indicate that miR-4497 may play a suppressive role in LSCC by targeting GBX2, which offer new insights into the tumorigenesis of LSCC. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Chen, Xudong AU - Chen X AD - Department of Otolaryngology, The First Hospital of Ningbo, Ningbo, People's Republic of China. FAU - Zhang, Litao AU - Zhang L AD - Department of Otolaryngology, The First Hospital of Ningbo, Ningbo, People's Republic of China. FAU - Tang, Shixiong AU - Tang S AD - Department of Otolaryngology, The First Hospital of Ningbo, Ningbo, People's Republic of China. Electronic address: wizardcxd@163.com. LA - eng PT - Journal Article DEP - 20180526 PL - Netherlands TA - Auris Nasus Larynx JT - Auris, nasus, larynx JID - 7708170 RN - 0 (BCL2 protein, human) RN - 0 (BCL2L1 protein, human) RN - 0 (GBX2 protein, human) RN - 0 (Homeodomain Proteins) RN - 0 (MCL1 protein, human) RN - 0 (MIRN4497 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Myeloid Cell Leukemia Sequence 1 Protein) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Messenger) RN - 0 (bcl-X Protein) SB - IM MH - Apoptosis/genetics MH - Blotting, Western MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Cell Survival/genetics MH - Colony Count, Microbial MH - Flow Cytometry MH - Homeodomain Proteins/*genetics/metabolism MH - Humans MH - Laryngeal Neoplasms/*genetics/metabolism MH - MAP Kinase Signaling System MH - MicroRNAs/genetics/*physiology MH - Myeloid Cell Leukemia Sequence 1 Protein/genetics/metabolism MH - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism MH - RNA, Messenger/metabolism MH - Real-Time Polymerase Chain Reaction MH - Squamous Cell Carcinoma of Head and Neck/*genetics/metabolism MH - bcl-X Protein/genetics/metabolism OTO - NOTNLM OT - Apoptosis OT - GBX2 OT - Laryngeal squamous cell carcinoma (LSCC) OT - MAPKs OT - MiR-4497 EDAT- 2018/05/31 06:00 MHDA- 2019/06/14 06:00 CRDT- 2018/05/31 06:00 PHST- 2018/02/12 00:00 [received] PHST- 2018/04/08 00:00 [revised] PHST- 2018/05/08 00:00 [accepted] PHST- 2018/05/31 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2018/05/31 06:00 [entrez] AID - S0385-8146(18)30168-8 [pii] AID - 10.1016/j.anl.2018.05.005 [doi] PST - ppublish SO - Auris Nasus Larynx. 2019 Feb;46(1):106-113. doi: 10.1016/j.anl.2018.05.005. Epub 2018 May 26.