LMNA Knock-Down Affects Differentiation and Progression of Human Neuroblastoma Cells

Maresca, Giovanna; Natoli, Manuela; Nardella, Marta; Arisi, Ivan; Trisciuoglio, Daniela; Desideri, Marianna; Brandi, Rossella; D’Aguanno, Simona; Nicotra, Maria Rita; D’Onofrio, Mara; Urbani, Andrea; Natali, Pier Giorgio; Bufalo, Donatella Del; Felsani, Armando; D’Agnano, Igea

doi:10.1371/journal.pone.0045513

Cited by 43 publications

(35 citation statements)

References 44 publications

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“…Among the 20 proteins, HUWE1, PCNA, GSN, ANXA1, AKAP12, and IDH2 have major roles in osteosarcoma tumorigenesis121314151617. MTHFD1, TSTA3, PGK1, HSPB1, MPST, HADHA, MCM5, CSE1L, LMNA, and MACF1 have been reported to be involved in tumorigenesis but not in osteosarcoma18192021222324252627. ACOT1, KTN1, DARS, and PROSC have not been reported in tumorigenesis.…”

Section: Resultsmentioning

confidence: 99%

CSE1L interaction with MSH6 promotes osteosarcoma progression and predicts poor patient survival

Cheng

Lin

et al. 2017

Sci Rep

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To discover tumor-associated proteins in osteosarcoma, a quantitative proteomic analysis was performed to identify proteins that were differentially expressed between osteosarcoma and human osteoblastic cells. Through clinical screening and a functional evaluation, chromosome segregation 1-like (CSE1L) protein was found to be related to the growth of osteosarcoma cells. To date, little is known about the function and underlying mechanism of CSE1L in osteosarcoma. In the present study, we show that knockdown of CSE1L inhibits osteosarcoma growth in vitro and in vivo. By co-immunoprecipitation and RNA-seq analysis, CSE1L was found to interact with mutS homolog 6 (MSH6) and function as a positive regulator of MSH6 protein in osteosarcoma cells. A rescue study showed that decreased growth of osteosarcoma cells by CSE1L knockdown was reversed by MSH6 overexpression, indicating that the activity of CSE1L was an MSH6-dependent function. In addition, depletion of MSH6 hindered cellular proliferation in vitro and in vivo. Notably, CSE1L expression was correlated with MSH6 expression in tumor samples and was associated with poor prognosis in patients with osteosarcoma. Taken together, our results demonstrate that the CSE1L-MSH6 axis has an important role in osteosarcoma progression.

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Section: Resultsmentioning

confidence: 99%

CSE1L interaction with MSH6 promotes osteosarcoma progression and predicts poor patient survival

Cheng

Lin

et al. 2017

Sci Rep

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“…Primers for VDAC1, TROVE2, PSAP, MYO1B, TOMM22, MTHFD1, HTT, HIST1H4A, RPS13, MOCOS, BUB1 and GAPDH were selected from the PrimerBank database [43]. Primer sequence for BUB3, BUBR1, LMNA and CALM1 were selected from respective references [39, 40, 44, 45]. All the primer sequences used in this study are listed in Supplementary Table 2.…”

Section: Methodsmentioning

confidence: 99%

Novel downstream molecular targets of SIRT1 in melanoma: A quantitative proteomics approach

et al. 2014

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Melanoma is one of the most lethal forms of skin cancer and its incidence is continuing to rise in the United States. Therefore, novel mechanism and target-based strategies are needed for the management of this disease. SIRT1, a NAD(+)-dependent class III histone deacetylase, has been implicated in a variety of physiological processes and pathological conditions. We recently demonstrated that SIRT1 is upregulated in melanoma and its inhibition by a small-molecule, tenovin-1, inhibits cell proliferation and clonogenic survival of melanoma cells, possibly via activating p53. Here, we employed a gel free quantitative proteomics approach to identify the downstream effectors and targets of SIRT1 in melanoma. The human malignant melanoma, G361 cells were treated with tenovin-1 followed by protein extraction, in liquid trypsin digestion, and peptide analyses using nanoLC-MS/MS. A total of 1091 proteins were identified, of which 20 proteins showed significant differential expression with 95% confidence interval. These proteins were subjected to gene ontology and Ingenuity Pathway Analysis (IPA) to obtain the information regarding their biological and molecular functions. Real-Time qRT-PCR validation showed that five of these (PSAP, MYO1B, MOCOS, HIS1H4A and BUB3) were differentially expressed at mRNA levels. Based on their important role in cell cycle regulation, we selected to focus on BUB family proteins (BUB3, as well as BUB1 and BUBR1) for subsequent validation. The qRT-PCR and immunoblot analyses showed that tenovin-1 inhibition of SIRT1 resulted in a downregulation of BUB3, BUB1 and BUBR1 in multiple melanoma cell lines. Since tenovin-1 is an inhibitor of both SIRT1 and SIRT2, we employed lentivirus mediated silencing of SIRT1 and SIRT2 in G361 cells to determine if the observed effects on BUB family proteins are due to SIRT1- or SIRT2- inhibition. We found that only SIRT1 inhibition resulted in a decrease in BUB3, BUB1 and BUBR1. Our study identified the mitotic checkpoint regulator BUB family proteins as novel downstream targets of SIRT1. However, further validation is needed in appropriate models to confirm our findings and expand on our observations.

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“…The inability to differentiate is further indicated by the absence of distinctive neurites outgrowth and reduced expression of neural markers. 28 Collectively, the studies indicate that reduced levels of lamin A/C expression could be used as a diagnostic tool for the more aggressive form of neuroblastoma.…”

Section: Role Of Lamins In Neuroblastomamentioning

confidence: 97%

A novel role of lamins from genetic disease to cancer biomarkers

Sakthivel¹,

Sehgal²

2016

Oncol Rev

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Lamins are the key components of the nuclear lamina and by virtue of their interactions with chromatin and binding partners act as regulators of cell proliferation and differentiation. Of late, the diverse roles of lamins in cellular processes have made them the topic of intense debate for their role in cancer progression. The observations about aberrant localization or misexpression of the nuclear lamins in cancerous tissues have often led to the speculative role of lamins as a cancer risk biomarker. Here we discuss the involvement of lamins in several cancer subtypes and their potential role in predicting the tumor progression.

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LMNA Knock-Down Affects Differentiation and Progression of Human Neuroblastoma Cells

Cited by 43 publications

References 44 publications

CSE1L interaction with MSH6 promotes osteosarcoma progression and predicts poor patient survival

CSE1L interaction with MSH6 promotes osteosarcoma progression and predicts poor patient survival

Novel downstream molecular targets of SIRT1 in melanoma: A quantitative proteomics approach

A novel role of lamins from genetic disease to cancer biomarkers

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