Expression of the monocyte chemotactic protein-1-induced protein 1 decreases human neuroblastoma cell survival

Skalniak, Anna; Boratyn, Elżbieta; Tyrkalska, Sylwia D.; Horwacik, Irena; Durbas, Małgorzata; Łastowska, Maria; Jura, Jolanta; Rokita, Hanna

doi:10.3892/or.2014.3076

Cited by 25 publications

(35 citation statements)

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“…There is growing evidence that MCPIP1 plays a role during the process of tumorigenesis. It has been already demonstrated that MCPIP1 regulates the viability and proliferation of neuroblastoma (20), HeLa, HepG2 (19), ccRCC (25), and breast cancer cells (21). Previous findings have demonstrated that MCPIP1 degrades the mRNA of antiapoptotic gene transcripts in breast cancer cells, leading to apoptosis and tumor regression (22).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, MCPIP1 is a negative regulator of NFkB activity (11,16,17) and may suppress miRNA biosynthesis (18). Recently, it has been shown that MCPIP1 is involved in the regulation of viability and proliferation in numerous cancer cell lines (19)(20)(21). Moreover, MCPIP1 overexpression in breast cancer cells induces apoptosis in vitro and reduces tumor growth and metastatic disease in vivo (22).…”

Section: Introductionmentioning

confidence: 99%

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MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression

et al. 2017

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Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFkB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patientderived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VEcadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression

et al. 2017

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“…Treatment of HeLa and HepG2 cells with proteasome inhibitor MG-132 reduces cell viability along with MCPIP1 expression (22). In human neuroblastoma cells MCPIP1 overexpression decreases cell viability and proliferation (23). MCPIP1 also stabilizes RGS2 protein through its deubiquitinase activity to suppress breast cancer cell growth (24).…”

Section: Introductionmentioning

confidence: 99%

MCPIP1 Selectively Destabilizes Transcripts Associated with an Antiapoptotic Gene Expression Program in Breast Cancer Cells That Can Elicit Complete Tumor Regression

Ning

et al. 2016

Cancer Research

104

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The ability of cancer cells to evade apoptosis is dictated by a shift in the balance between pro- and anti-apoptotic gene expression programs. Monocyte chemotactic protein induced protein 1 (MCPIP1) is a zinc finger RNA binding protein with important roles in mediating inflammatory responses. Overexpression of MCPIP1 in different cancer cell types has been implicated in eliciting an antitumor response, but a direct role of MCPIP1 in apoptosis has not been established. In this study, we demonstrate that MCPIP1 functions as a potent tumor suppressor that induces apoptosis of breast tumor cells by selectively enhancing mRNA decay of anti-apoptotic gene transcripts including Bcl2L1, Bcl2A1, RelB, Birc3, and Bcl3. Mechanistically, MCPIP1 physically interacted with a stem-loop structure in the 3'UTR of these transcripts through its PIN domain, causing mRNA destabilization. Furthermore, we found that MCPIP1 expression was repressed in breast tumor cells, and overexpression of MCPIP1 induced apoptosis, whereas its depletion enhanced cancer cell proliferation. Moreover, MCPIP1 induction in vivo resulted in complete regression of established tumors and a significant reduction in metastatic disease. Notably, low MCPIP1 expression in tumor samples from breast cancer patients was strongly associated with poor survival over 13 years of follow up. Collectively, our results highlight MCPIP1 is a new tumor suppressor in breast cancer that induces cell death by tipping the balance in favor of pro-apoptotic gene expression.

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“…Our recent analysis of microarray data showed a lack of expression of the MCPIP1 transcript in primary neuroblastoma and low expression of the gene in several human neuroblastoma cell lines [Skalniak et al, ]. Enforced MCPIP1 expression in BE(2)‐C human neuroblastoma cells caused a significant decrease in neuroblastoma proliferation and metabolic status [Skalniak et al, ], as well as changes of expression levels of several protein‐coding gene transcripts, prevalently involved in RNA and DNA metabolism and a few microRNAs [Boratyn et al, ].…”

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confidence: 99%

“…First, concerns repression of the monocyte chemoattractant protein‐1 (MCP1), which is a known chemokine and one of the inducers of MCPIP1 synthesis, by MYCN [Huang and Weiss, ]. Hence, in MYCN ‐amplified neuroblastoma cells the phenomenon might be responsible for the observed lack of MCPIP1 expression [Skalniak et al, ]. Another explanation of inverse correlation between MYCN and MCPIP1 levels may derive from data documenting microRNA‐9‐mediated suppression of MCPIP1 transcript, as miR‐9 can be directly induced by MYCN [Ma et al, ].…”

mentioning

confidence: 99%

MCPIP1 Exogenous Overexpression Inhibits Pathways Regulating MYCN Oncoprotein Stability in Neuroblastoma

Boratyn

Nowak

Durbas

et al. 2017

J of Cellular Biochemistry

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The main physiological function of MCPIP1 (regnase-1) is negative regulation of inflammation. Moreover, roles of regnase-1 in apoptosis and differentiation have also been described, but its involvement in cancer is yet to be fully recognized. Earlier, we showed a lack of expression of MCPIP1 in both primary tumors and several neuroblastoma cell lines. Additionally, we reported that levels of MCPIP1 and the key neuroblastoma oncoprotein-MYCN were inversely correlated in BE(2)-C clones overexpressing the MCPIP1 gene. Here, we show that exogenous expression of the MCPIP1 protein decreases MYCN mRNA and protein levels without changing the MYCN mRNA half-life. Furthermore, it was shown that MCPIP1-wt exogenous expression affects levels and phosphorylation of MYCN partners such as Aurora A (Thr288), CDC2 (Tyr15 and Thr161), GSK3β (Ser9), and key cellular components of Akt/mTOR signaling, which regulate MYCN stability and activation. In accordance with the obtained results, we found increased phosphorylation of MYCN protein at Thr58 that causes destabilization of the oncoprotein. Moreover, it is shown that exogenous expression of MCPIP1 does not cause apoptosis. Our data extend knowledge on roles of MCPIP1 in our model and link the protein to regulation of expression and stability of MYCN through decrease of signaling via Akt/mTOR pathway. J. Cell. Biochem. 118: 1741-1755, 2017. © 2016 Wiley Periodicals, Inc.

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Expression of the monocyte chemotactic protein-1-induced protein 1 decreases human neuroblastoma cell survival

Cited by 25 publications

References 35 publications

MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression

MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression

MCPIP1 Selectively Destabilizes Transcripts Associated with an Antiapoptotic Gene Expression Program in Breast Cancer Cells That Can Elicit Complete Tumor Regression

MCPIP1 Exogenous Overexpression Inhibits Pathways Regulating MYCN Oncoprotein Stability in Neuroblastoma

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