Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via TGF-&amp;beta;/Smad2/3 signaling pathway in bladder cancer cells

Chen, Wei; Zhao, Kai; Miao, Chenkui; Xu, Aiming; Zhang, Jianzhong; Zhu, Jingjing; Su, Shifeng; Wang, Zengjun

doi:10.2147/ott.s130139

Cited by 40 publications

(24 citation statements)

References 32 publications

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“…TRIM59 has now been accepted as an important oncoprotein, and the molecular mechanisms for its tumor-promoting functions are very preliminary. Previous studies proved that TRIM59 could also affect the TP53 pathway, SMAD2/3 pathway and AKT pathway [11,[44][45][46]. These findings together with ours indicated that TRIM59 has many profound functions including the effect on autophagy, and these functions are important for cancer progression.…”

Section: Discussionsupporting

confidence: 80%

TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1

et al. 2018

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Macroautophagy/autophagy is a multistep cellular process that sequesters cytoplasmic components for lysosomal degradation. BECN1/Beclin1 is a central protein that assembles cofactors for the formation of a BECN1-PIK3C3-PIK3R4 complex to trigger the autophagy protein cascade. Discovering the regulators of BECN1 is important for understanding the mechanism of autophagy induction. Here, we demonstrate that TRIM59, a tripartite motif protein, plays an important role in autophagy regulation in non-small cell lung cancer (NSCLC). On the one hand, TRIM59 regulates the transcription of BECN1 through negatively modulating the NFKB pathway. On the other hand, TRIM59 regulates TRAF6 induced K63-linked ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3 complex. We further demonstrate that TRIM59 can mediate K48-linked ubiquitination of TRAF6 and promote the proteasomal degradation of TRAF6. Taken together, our findings reveal novel dual roles for TRIM59 in autophagy regulation by affecting both the transcription and the ubiquitination of BECN1. Abbreviations: ACTB: actin beta; BECN1: beclin 1; CHX: cycloheximide; CQ: chloroquine; GFP: green fluorescent protein; HA: haemagglutinin tag; His: polyhistidine tag; LC3B: microtubule associated protein 1 light chain 3 beta; NFKB: nuclear factor kappa B; NFKBIA: NFKB inhibitor alpha; NSCLC: non-small cell lung cancer; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; RELA: RELA proto-oncogene, NF-kB subunit; SQSTM1: sequestosome 1; tGFP: Turbo green fluorescent protein; TRAF6: TNF receptor associated factor 6; TRIM59: tripartite motif containing 59; B: ubiquitin.

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Section: Discussionsupporting

confidence: 80%

TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1

et al. 2018

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“…Trim59, the expression of which is upregulated in bladder tumors, promotes proliferation, EMT, migration, and invasion of bladder cancer cells. Silencing of Trim59 attenuates migration and invasion of bladder cancer cells while the presence of TGF-β1 relieves the suppressive effect of Trim59 knock-out [212].…”

Section: Bladder Cancermentioning

confidence: 99%

TGF-β and microRNA Interplay in Genitourinary Cancers

Bogusławska¹,

Kryst

Poletajew

et al. 2019

Cells

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Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.

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“…Current research focused on the function of TRIM59 in various types of cancer and has demonstrated that TRIM59 can regulate the PI3K/AKT signal pathway in various cancers. TRIM59 promotes neuroblastoma through the Wnt/beta-catenin (24) and PI3K/AKT signaling pathways (18), accelerates bladder cancer via the TGF-beta/Smad2/3 signaling pathway (25), and facilitates breast cancer (26), cholangiocarcinoma (17,19), and ovarian cancer (27) through the PI3K/AKT signaling pathway. PI3K/AKT is also related to inflammation by activating IKKα and the whole NF-κB signal pathway (20).…”

Section: Discussionmentioning

confidence: 99%

TRIM59 Protects Mice From Sepsis by Regulating Inflammation and Phagocytosis in Macrophages

et al. 2020

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Sepsis is associated with bacterial invasion and inflammation and has a high mortality rate. Previous studies have demonstrated that tripartite motif 59 (TRIM59) was involved in NF-κB signaling and could promote phagocytosis of macrophages, but the role of TRIM59 in sepsis is still unknown. In our study, we found that TRIM59 was downregulated in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs). In the cecal ligation and puncture (CLP) sepsis mice model, the mortality of Trim59 flox/flox Lyz-Cre (Trim59-cKO) mice was higher, the immune cell infiltration and damage of liver and lung were more severe, and bacteria burden was increased. We also found that TRIM59 altered the production of pro-inflammation cytokines, as well as macrophage phagocytosis ability. Further analysis indicated that NF-κB signal pathway and Fcγ receptors might be involved in these regulations. Our study demonstrated for the first time that TRIM59 protects mice from sepsis by regulating inflammation and phagocytosis in macrophages.

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Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via TGF-β/Smad2/3 signaling pathway in bladder cancer cells

Cited by 40 publications

References 32 publications

TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1

TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1

TGF-β and microRNA Interplay in Genitourinary Cancers

TRIM59 Protects Mice From Sepsis by Regulating Inflammation and Phagocytosis in Macrophages

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