FHOD3 promotes carcinogenesis by regulating RhoA/ROCK1/LIMK1 signaling pathway in medulloblastoma
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RESEARCH ARTICLE
FHOD3 promotes carcinogenesis by regulating RhoA/ROCK1/LIMK1 signaling pathway in medulloblastoma J. Yu1 · W. Shi1 · R. Zhao1 · W. Shen1 · H. Li1 Received: 23 January 2020 / Accepted: 10 May 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
Abstract Purpose Medulloblastoma (MB) is a malignant brain disease in young children. The overall survival of MB patients is disappointing due to absence of effective therapeutics and this could be attributed to the lack of molecular mechanism underlying MB. FHOD3 was an important gene during cardio-genesis and was reported to promote cell migration in cancer. However, its role in MB is not clear to date. Methods RT-qPCR and IHC analysis were used to determine expression of FHOD3. Survival curve was drawn by K–M analysis. FHOD3 was knocked down by RNAi technology. The effects of FHOD3 on medulloblastoma cells were determined by CCK-8 assay, colony formation assay, transwell assay and FACs analysis. Results FHOD3 expression increased by 1.5 fold in tumor tissues compared to the control and IHC analysis further confirmed strong expression of FHOD3 in medulloblastoma tissues. Then higher FHOD3 expression was associated with shorter survival time in MB patients (13.0 months versus 43.8 months). In medulloblastoma cells such as Daoy and D283med, FHOD3 also displayed abundant expression. When FHOD3 was knocked down, the ability of cell proliferation and colony formation was reduced over greatly. The capability of cell migration and invasion was also inhibited significantly. However, cell apoptotic rate increased significantly reversely. Mechanistically, the phosphorylation level of RhoA, ROCK1, and LIMK1 was decreased when FHOD3 was knocked down but increased reversely when FHOD3 was over-expressed in Daoy cells. Conclusions FHOD3 was associated with overall survival time in medulloblastoma patients and was essential to cell proliferation, growth and survival in medulloblastoma and might regulates activation of RhoA/ROCK1/LIMK1 signaling pathway. Keywords FHOD3 · RhoA · ROCK1 · Medulloblastoma
Introduction Formin homology proteins are regulator of actin protein and function as scaffold in a series of processes such as organogenesis, homeostasis, cancer cell invasion, and so on [1]. FHOD3, also known as FHOS2 or Formactin2, was an important member of Formin homology proteins and was mapped at chromosome 18q12.2 region [1]. FHOD3 was originally demonstrated to play important role in cardiogenesis and in function of heart. For example, FHOD3 was reported to regulate actin assembly and sarcomere organization in striated muscle [2]. FHOD3 organized myofibrillogenesis in cardio-genesis and maintained the contractile * H. Li [email protected] 1
Department of Neurosurgery, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, China
filaments of cardiomyocytes [3, 4]. However, aberrant FHOD3 caused a list of cardiac diseases such as hypertrophic cardiomyopathy [5, 6]. FHOD3 was considered as genetic basis for hypertrophic
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