Tumor-suppressive Maspin Functions as a Reactive Oxygen Species Scavenger

Mahajan, Nitin; Shi, Heidi Y.; Lukas, Thomas J.; Zhang, Ming

doi:10.1074/jbc.m112.410852

Cited by 14 publications

(15 citation statements)

References 45 publications

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“…Cellular debris was cleared from lysates by centrifugation, and the protein concentration was determined by the bicinchoninic acid (BCA) protein assay (Pierce, Rockford, IL, USA). Samples were separated on precast 4–15% Tris‐glycine extended‐PAGE (Bio‐Rad), transferred to a PVDF membrane (Bio‐Rad), blotted with the indicated antibodies, and visualized with enhanced chemiluminescence substrate (Pierce) (21).…”

Section: Methodsmentioning

confidence: 99%

Sabotaging of the oxidative stress response by an oncogenic noncoding RNA

Mahajan

Bennett

et al. 2016

FASEB j.

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Overexpression of the multiple myeloma set domain (MMSET) Wolf-Hirschhorn syndrome candidate 1 gene, which contains an orphan box H/ACA class small nucleolar RNA, ACA11, in an intron, is associated with several cancer types, including multiple myeloma (MM). ACA11 and MMSET are overexpressed cotranscriptionally as a result of the t(4;14) chromosomal translocation in a subset of patients with MM. RNA sequencing of CD138 tumor cells from t(4;14)-positive and -negative MM patient bone marrow samples revealed an enhanced oxidative phosphorylation mRNA signature. Supporting these data, ACA11 overexpression in a t(4;14)-negative MM cell line, MM1.S, demonstrated enhanced reactive oxygen species (ROS) levels. In addition, an enhancement of cell proliferation, increased soft agar colony size, and elevated ERK1/2 phosphorylation were observed. This ACA11-driven hyperproliferative phenotype depended on increased ROS levels as exogenously added antioxidants attenuate the increased proliferation. A major transcriptional regulator of the cellular antioxidant response, nuclear factor (erythroid-derived 2)-like 2 (NRF2), shuttled to the nucleus, as expected, in response to ACA11-driven increases in ROS; however, transcriptional up-regulation of some of NRF2's antioxidant target genes was abrogated in the presence of ACA11 overexpression. These data show for the first time that ACA11 promotes proliferation through inhibition of NRF2 function resulting in sustained ROS levels driving cancer cell proliferation.-Mahajan, N., Wu, H.-J., Bennett, R. L., Troche, C., Licht, J. D., Weber, J. D., Maggi, L. B., Jr., Tomasson, M. H. Sabotaging of the oxidative stress response by an oncogenic noncoding RNA.

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Section: Methodsmentioning

confidence: 99%

Sabotaging of the oxidative stress response by an oncogenic noncoding RNA

Mahajan

Bennett

et al. 2016

FASEB j.

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“…Reduction in cell proliferation with an increased rate of apoptosis is well described in different cancer cells [18]. We next measured the rate of apoptosis in OS cells in the presence of miR-9 inhibitor.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of miR-9 decreases osteosarcoma cell proliferation

Wei

Huang

et al. 2019

Bosn J of Basic Med Sci

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Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults. Disruption of microRNA (miRNA) regulation is well established in the pathophysiology of different cancers, including OS. Increased expression of miR-9 in OS positively correlates with the tumor size, clinical stage, and distant metastasis. In the present study, we used two different OS cell lines, MG-63 and Saos-2, as in vitro models. Small interfering RNA against miR-9 and miR-9 mimics were used to study the function of miR-9 in these two cell lines. We determined the effect of miR-9 inhibition on cell proliferation, cell cycle, apoptosis, and the protein expression of different genes. Our results demonstrated that miR-9 knockdown in the human OS cell lines inhibits their metastatic potential, as determined by decreased cell proliferation and cell cycle arrest, decreased invasion, and increased apoptosis. The western blot analysis showed that cadherin-1 (CDH1), matrix metalloproteinase 13 (MMP-13), forkhead box O3 (FOXO3a), Bcl-2-like protein 11 (BCL2L11), and β-catenin (CTNNB1) are involved in miR-9 signaling. Moreover, miR-9 mimics rescued the effects caused by the inhibition of miR-9 in the OS cell lines. Our findings suggest that miR-9 is important for mediating OS cell migration, invasion, metastasis, and apoptosis. Inhibition of miR-9 could be further explored as a therapeutic target to treat OS.

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“…Serpins (serine protease inhibitors) represent the largest family of protease inhibitors and are found in all higher eukaryotes and some bacteria, archaea and viruses (Olson & Gettins, 2011;Silverman et al, 2010). Proteolytic events are integral to a wide variety of signaling pathways and govern diverse physiological functions, such as development (Hashimoto et al, 2003;Ligoxygakis et al, 2003;Francis et al, 2012), coagulation (Huntington, 2013), cell migration (Ravenhill et al, 2010;Declerck & Gils, 2013;Yamamoto et al, 2013;Huasong et al, 2015), tumor suppression (Mahajan et al, 2013), fibrinolysis (Rau et al, 2007;Al-Horani, 2014) and immunity (Ashton-Rickardt, 2013;Silverman et al, 2010;Gatto et al, 2013). In general, the proteases that comprise these signaling pathways are expressed as zymogens, becoming activated upon proteolytic cleavage in order to elicit a rapid, controlled physiological response.…”

Section: Introductionmentioning

confidence: 99%

1.45 Å resolution structure of SRPN18 from the malaria vectorAnopheles gambiae

Meekins¹,

Zhang²,

Battaile³

et al. 2016

Acta Cryst Sect F

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Serine protease inhibitors (serpins) in insects function within development, wound healing and immunity. The genome of the African malaria vector, Anopheles gambiae, encodes 23 distinct serpin proteins, several of which are implicated in disease-relevant physiological responses. A. gambiae serpin 18 (SRPN18) was previously categorized as non-inhibitory based on the sequence of its reactive-center loop (RCL), a region responsible for targeting and initiating protease inhibition. The crystal structure of A. gambiae SRPN18 was determined to a resolution of 1.45 Å, including nearly the entire RCL in one of the two molecules in the asymmetric unit. The structure reveals that the SRPN18 RCL is extremely short and constricted, a feature associated with noncanonical inhibitors or non-inhibitory serpin superfamily members. Furthermore, the SRPN18 RCL does not contain a suitable protease target site and contains a large number of prolines. The SRPN18 structure therefore reveals a unique RCL architecture among the highly conserved serpin fold.

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Tumor-suppressive Maspin Functions as a Reactive Oxygen Species Scavenger

Cited by 14 publications

References 45 publications

Sabotaging of the oxidative stress response by an oncogenic noncoding RNA

Sabotaging of the oxidative stress response by an oncogenic noncoding RNA

Inhibition of miR-9 decreases osteosarcoma cell proliferation

1.45 Å resolution structure of SRPN18 from the malaria vectorAnopheles gambiae

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