SENP1 activity sustains cancer stem cell in hypoxic HCC

Conigliaro, Alice; Tripodi, Marco; Parola, Maurizio

doi:10.1136/gutjnl-2017-313946

Cited by 9 publications

(8 citation statements)

References 13 publications

(15 reference statements)

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“…HCC is fundamentally manifested with alterations in proteins that support tumor growth. (36) GNAO1, whose deregulation was previously found in epileptic encephalopathy and movement disorder, is screened and validated to be an HCC suppressor gene by our group. (37) The depletion of FTO or other m 6 A erasers is generally believed to result in the production of more abundant mRNA copies and expression of target proteins, but the actual effect on the expression of m 6 A target proteins has been a long-standing puzzle in the field.…”

Section: Discussionmentioning

confidence: 99%

SIRT1 Regulates N6‐Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2‐Dependent FTO SUMOylation

et al. 2020

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BaCKgRoUND aND aIMS: Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase silent information regulator 1 (SIRT1) was discovered in HCC, and its presence is positively correlated with malignancy and metastasis. N 6-methyladenosine (m 6 A) is the most prominent modification, but the exact mechanisms on how SIRT1 regulates m 6 A modification to induce hepatocarcinogenesis remain unclear. appRoaCH aND ReSUltS: Here we demonstrate that SIRT1 exerts an oncogenic role by down-regulating fat mass and obesity-associated protein (FTO), which is an m 6 A demethylase. A crucial component of small ubiquitin-related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1, and it is indispensable for FTO SUMOylation at Lysine (K)-216 site that promotes FTO degradation. Moreover, Guanine nucleotide-binding protein G (o) subunit alpha (GNAO1) is identified as m 6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m 6 A + GNAO1 and down-regulates its mRNA expression. CoNClUSIoNS: We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m 6 A + of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a target of SIRT1 for therapeutic agents to treat HCC.

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Section: Discussionmentioning

confidence: 99%

SIRT1 Regulates N6‐Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2‐Dependent FTO SUMOylation

et al. 2020

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“…Hypoxia‐inducible factor‐1 alpha activates downstream glycolytic enzyme‐encoding genes and promotes glycolysis and glucose metabolism, epithelial‐mesenchymal transition (EMT), and tumor metastasis . The overexpression of HIF‐1α is well known to be correlated with the poor overall survival of several cancers .…”

Section: Introductionmentioning

confidence: 99%

“…The overexpression of HIF‐1α is well known to be correlated with the poor overall survival of several cancers . The stable activity of SENP1 under hypoxia‐stressed hepatocellular carcinoma could sustain cancer stem cell stemness by promoting deSUMOylation and stabilization of HIF‐1α . SENP1 expression desensitizes cancer cells to chemoradiotherapy via the upregulation of HIF‐1α .…”

Section: Introductionmentioning

confidence: 99%

“…13 Hypoxia-inducible factor-1 alpha activates downstream glycolytic enzyme-encoding genes and promotes glycolysis and glucose metabolism, epithelial-mesenchymal transition (EMT), and tumor metastasis. 9,[14][15][16][17] The overexpression of HIF-1α is well known to be correlated with the poor overall survival of several cancers. 18,19 The stable activity of SENP1 under hypoxia-stressed hepatocellular carcinoma could sustain cancer stem cell stemness by promoting deSUMOylation and stabilization of HIF-1α.…”

mentioning

confidence: 99%

“…18,19 The stable activity of SENP1 under hypoxia-stressed hepatocellular carcinoma could sustain cancer stem cell stemness by promoting deSUMOylation and stabilization of HIF-1α. 17,20 SENP1 expression desensitizes cancer cells to chemoradiotherapy via the upregulation of HIF-1α. 21 Vascular endothelial growth factor (VEGF) is a target of HIF-1α, and the activation of HIF-1α/VEGF signaling pathway is essential for angiogenesis, tumor angiogenesis, atherosclerosis, and diabetes mellitus.…”

mentioning

confidence: 99%

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Small ubiquitin‐like modifier/sentrin‐specific peptidase 1 associates with chemotherapy and is a risk factor for poor prognosis of non‐small cell lung cancer

Liu

Zhang

Wang

2018

Clinical Laboratory Analysis

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When compared with adjacent non-tumor tissues, the overexpression of SENP1 mRNA and protein in NSCLC tumor tissues was determined using qRT-PCR and immunochemistry. Based on the chemoradiotherapy response rate, we found that NSCLC patients with higher SENP1 expression showed lower rates of complete response and higher partial and non-response rate to chemoradiotherapy. In the overall survival analysis, we found patients with high SENP1 expression showed significant shorter survival time compared with those with low SENP1 expression. In the multivariate Cox regression model, we found SENP1 overexpression, TNM stage, and lymph metastasis were independent risk factors for poor prognosis of NSCLC. SENP1 overexpression contributed to chemoradiotherapy resistance of NSCLC. The overexpression of SENP1 could be used as a risk factor for the poor prognosis of NSCLC.

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SENP1 participates in Irinotecan resistance in human colon cancer cells

Chen

Nhan

Hsu

et al. 2021

J of Cellular Biochemistry

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Colorectal cancer is one of the most prevalent cancers in the world.Chemoresistance has always been a problem encountered in its treatment. It is known that SUMOylation may regulate protein stability and decomposition, and even affect the protein translocation and posttranslational modification in cells. Sentrin-specific protease 1 (SENP1) is involved in the maturation of SUMO protein, and on the other hand, plays a role in deSUMOylation, which dissociates the target protein from SUMO and prevents further degradation of the target protein. In this study, we established an Irinotecan (CPT-11) resistant human colon cancer LoVo strain (LoVo R- ) to investigate the role

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SENP1 activity sustains cancer stem cell in hypoxic HCC

Cited by 9 publications

References 13 publications

SIRT1 Regulates N6‐Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2‐Dependent FTO SUMOylation

SIRT1 Regulates N6‐Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2‐Dependent FTO SUMOylation

Small ubiquitin‐like modifier/sentrin‐specific peptidase 1 associates with chemotherapy and is a risk factor for poor prognosis of non‐small cell lung cancer

SENP1 participates in Irinotecan resistance in human colon cancer cells

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