PMID- 30720112 OWN - NLM STAT- MEDLINE DCOM- 20190816 LR - 20211209 IS - 1791-2423 (Electronic) IS - 1019-6439 (Print) IS - 1019-6439 (Linking) VI - 54 IP - 4 DP - 2019 Apr TI - Upregulation of microRNA‑194‑5p inhibits hypopharyngeal carcinoma cell proliferation, migration and invasion by targeting SMURF1 via the mTOR signaling pathway. PG - 1245-1255 LID - 10.3892/ijo.2019.4711 [doi] AB - Hypopharyngeal carcinoma (HPC) is an aggressive malignancy with the worst prognosis among all head and neck cancers. MicroRNAs (miRNAs) are involved in the development of many human cancers, and may function as oncogenes or tumor suppressors. The present study aimed to evaluate the effects of miRNA (miR)‑194‑5p on the proliferation and invasion of HPC cells and to identify the potential regulatory mechanism. First, miR‑194‑5p and Smad ubiquitin regulatory factor 1 (SMURF1) expression levels were examined in HPC tissues. Subsequently, to explore the effects of miR‑194‑5p on SMURF1, a dual‑luciferase reporter gene assay was performed to verify the target relationship. To define the role of miR‑194‑5p in HPC progression, miR‑194‑5p upregulation and depletion were used to evaluate its effects on cell viability, invasion and migration. SMURF1 silencing and rapamycin [an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway] treatment were also used to analyze the regulatory mechanism in HPC. Finally, tumor growth was assessed in xenografted tumors in nude mice. SMURF1 was demonstrated to be highly expressed, whereas miR‑194‑5p was poorly expressed in HPC tissues; SMURF1 was identified as a target gene of miR‑194‑5p. FaDu hypopharyngeal squamous cell carcinoma cells treated with miR‑194‑5p mimics exhibited decreased viability, invasion and migration. The results indicated that miR‑194‑5p may inactivate the mTOR signaling pathway by targeting SMURF1. In addition, the in vivo experiments further verified these regulatory effects. These data suggested that miR‑194‑5p‑targeted SMURF1 inhibition may be involved in the disruption of HPC progression through the repression of the mTOR signaling pathway. FAU - Xu, Shan AU - Xu S AD - Department of Ear, Nose and Throat, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Hui, Lian AU - Hui L AD - Department of Ear, Nose and Throat, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Yang, Ning AU - Yang N AD - Department of Ear, Nose and Throat, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Wang, Yan AU - Wang Y AD - Department of Ear, Nose and Throat, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Zhao, Ning AU - Zhao N AD - Department of Ear, Nose and Throat, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Jiang, Xue-Jun AU - Jiang XJ AD - Department of Ear, Nose and Throat, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. LA - eng PT - Journal Article DEP - 20190204 PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (3' Untranslated Regions) RN - 0 (MIRN194 microRNA, human) RN - 0 (MicroRNAs) RN - EC 2.3.2.26 (SMURF1 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) MH - 3' Untranslated Regions MH - Aged MH - Animals MH - Carcinoma, Squamous Cell/genetics/metabolism/*pathology MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Hypopharyngeal Neoplasms/genetics/metabolism/*pathology MH - Male MH - Mice MH - MicroRNAs/*genetics MH - Middle Aged MH - Neoplasm Invasiveness MH - Neoplasm Transplantation MH - Signal Transduction MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/metabolism MH - Ubiquitin-Protein Ligases/*genetics MH - *Up-Regulation PMC - PMC6411369 OTO - NOTNLM OT - microRNA-194-5p OT - hypopharyngeal carcinoma OT - Smad ubiquitin regulatory factor 1 OT - mammalian target of rapamycin signaling pathway OT - proliferation OT - metastasis EDAT- 2019/02/06 06:00 MHDA- 2019/08/17 06:00 PMCR- 2019/02/04 CRDT- 2019/02/06 06:00 PHST- 2018/05/17 00:00 [received] PHST- 2018/11/23 00:00 [accepted] PHST- 2019/02/06 06:00 [pubmed] PHST- 2019/08/17 06:00 [medline] PHST- 2019/02/06 06:00 [entrez] PHST- 2019/02/04 00:00 [pmc-release] AID - ijo-54-04-1245 [pii] AID - 10.3892/ijo.2019.4711 [doi] PST - ppublish SO - Int J Oncol. 2019 Apr;54(4):1245-1255. doi: 10.3892/ijo.2019.4711. Epub 2019 Feb 4.