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Upregulation of microRNA?194?5p inhibits hypopharyngeal carcinoma cell proliferation, migration and invasion by targeting SMURF1 via the mTOR signaling pathway.

ABSTRACT: 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.

SUBMITTER: Xu S

PROVIDER: S-EPMC6411369 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Upregulation of microRNA‑194‑5p inhibits hypopharyngeal carcinoma cell proliferation, migration and invasion by targeting SMURF1 via the mTOR signaling pathway.

Xu Shan S Hui Lian L Yang Ning N Wang Yan Y Zhao Ning N Jiang Xue-Jun XJ

International journal of oncology 20190204 4

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 ...[more]

PMID: 30720112

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Project description:Retinoblastoma (RB) is one of the most common forms of childhood intraocular cancer. While the occurrence of RB is traditionally associated with dysregulation of the RB1 gene, efforts have been made to assess the role of several other pathways that may result in RB. The Notch signaling pathway has been identified as one of the sentinel pathways in retinal development and has been indicated to serve as a tumor suppressor. However, epigenetic modifications of the Notch signaling pathway, and their consequences on tumor establishment and progression, have received little attention. The present study attempted to elucidate the microRNA (miR)-mediated dysregulation of the Notch signaling pathway and its implications on tumor initiation. Upon recruitment of patients with RB (age, 4-25 months), the levels of miR-34b-5p were determined in tumor and adjacent healthy tissues. Simultaneously, the serum levels of miR-34b-5p were measured in tumor and healthy samples using reverse transcriptase-quantitative PCR (RT-qPCR). Binding of miR-34b-5p to Notch1 and Notch2 were confirmed bioinformatically. In vitro studies were performed in Y79 and Weri-Rb-1 RB cell lines. The cell lines were transfected with miR-34b-5p constructs and miR-34b-5p overexpression was confirmed using RT-qPCR. The impact of miR-34b-5p overexpression on cell growth and cancer stemness markers (Sox-2, Nanog, and CD133) was examined. The expression levels of Notch1 and Notch2 were evaluated in the presence of miR-34b-5p. The rescue of cell growth and cancer stemness phenotypes was evaluated by co-transfection of miR-34b-5p with Notch1 or Notch2. The results of the present study indicated that the expression levels of miR-34b-5p were reduced in patient tissues and serum samples compared with those in healthy tissues and samples. Notch1 and Notch2 expression level was negatively correlated with the expression level of miR-34b-5p. Overexpression of miR-34b-5p resulted in reduced cell proliferation, migration, invasion and cancer stemness compared with the control group. Further in vivo experiments confirmed the inhibitory effects of miR-34b-5p on RB cell proliferation. Upon co-transfection of miR-34b-5p with Notch1 or Notch2, these phenotypes were rescued with reversal of cell growth and tumor sphere formation. Collectively, the results indicated that miR-34b-5p functions as a tumor suppressor in RB via regulating the Notch signaling pathway. Therefore, miR-34b-5p may be explored for its utility as a therapeutic target in RB.

Dataset Information

Upregulation of microRNA?194?5p inhibits hypopharyngeal carcinoma cell proliferation, migration and invasion by targeting SMURF1 via the mTOR signaling pathway.

Publications

Upregulation of microRNA‑194‑5p inhibits hypopharyngeal carcinoma cell proliferation, migration and invasion by targeting SMURF1 via the mTOR signaling pathway.

Similar Datasets

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