Smarcd1 Inhibits the Malignant Phenotypes of Human Glioblastoma Cells via Crosstalk with Notch1
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Smarcd1 Inhibits the Malignant Phenotypes of Human Glioblastoma Cells via Crosstalk with Notch1 Yihao Zhu 1,2 & Handong Wang 1
&
Maoxing Fei 1 & Ting Tang 1 & Wenhao Niu 1 & Li Zhang 1
Received: 16 March 2020 / Accepted: 29 October 2020 # The Author(s) 2020
Abstract Smarcd1 is a component of an evolutionary conserved chromatin remodeling complex—SWI/SNF, which is involved in transcription factor recruitment, DNA replication, recombination, and repair. Suppression of the SWI/SNF complex required for cellular differentiation and gene regulation may be inducible for cell proliferation and tumorigenicity. However, the inhibitory role of Smarcd1 in human glioblastoma cells has not been well illustrated. Both U87 and U251 human glioblastoma cell lines were employed in the present study. The lentivirus-mediated gene knockdown and overexpression approach was conducted to determine the function of Smarcd1. The protein levels were tested by western blot, and the relative mRNA contents were detected by quantitative real-time PCR. Cell viability was tested by CCK-8 and colony-forming assay. Transwell assays were utilized to evaluate the motility and invasive ability. Flow cytometry was employed to analyze cell cycle and apoptosis. SPSS software was used for statistical analysis. Low expression of Smarcd1 was observed in glioblastoma cell lines and in patients with high-grade glioma. Importantly, the depletion of Smarcd1 promoted cell proliferation, invasion, and chemoresistance, whereas enhanced expression of Smarcd1 inhibited tumor-malignant phenotypes. Mechanistic research demonstrated that overexpression of Smarcd1 decreased the expression of Notch1, while knockdown of Notch1 increased the expression of Smarcd1 through Hes1 suppression. Hence, the crosstalk between Smarcd1 and Notch1, which formed a feedback loop, was crucial in regulation of glioblastoma malignant phenotypes. Furthermore, targeting Smarcd1 could be a potential strategy for human glioblastoma treatment. Keywords Smarcd1 . Glioblastoma . Proliferation . Migration . Chemoresistance . Notch1 signaling pathway
Abbreviations Smarcd1 SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 1 CCK-8 Cell Counting Kit-8 PCR Polymerase chain reaction
* Handong Wang [email protected] 1
Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu, People’s Republic of China
2
Department of Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, People’s Republic of China
Introduction Glioblastoma is the lethal primary brain tumor in the central nervous system (CNS). Despite aggressive treatments, namely accurate surgery accompanied by chemotherapy and radiotherapy, the prognosis remains dismal with a median survival of less than 20 months and patients with inevitable recurrence usually survive less than 12 months [1]. The 2016 World Health Organization classification of tumors in the CNS highlighted new
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