RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy

Wang, Hui; Wang, Yanan; Liu, Qian; Wang, Xue; Gu, Hailiang; Dong, Xiaoqiang; Huang, Shiqian; Jin, Min; Ge, Heng; Xu, Congfeng; Zhang, Yanyun

doi:10.18632/oncotarget.9433

Cited by 35 publications

(27 citation statements)

References 35 publications

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“…In addition, previous studies have revealed that autophagy is associated with tumor progression; the dietary intake of urolithin A inhibited the migration of CRC cells and the activity of matrix metalloproteinase-9 through inducing autophagy (22). In another study, RNF216 prevented autophagy in CRC cells through inhibiting the autophagy-associated gene Beclin-1 during nutritional starvation, thus promoting the proliferation and migration of CRC cells (23). Therefore, the aim of the present study was to further investigate these two mechanisms.…”

Section: Discussionmentioning

confidence: 93%

Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy

et al. 2020

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Autophagy plays a key role in colorectal cancer (CRC) development and reduces the sensitivity of CRC cells to treatment. The present study reported a novel tumor-suppressive role for autophagy, which was demonstrated to be regulated through the novel oncogene neurotrophin-4 (NTF4). NTF4 was significantly overexpressed in tumor tissue compared with non-tumor mucosa, and the upregulation of NTF4 in CRC was associated with poor overall survival and advanced TNM stage. The genetic knockdown of NTF4 using short hairpin RNA in CRC cells prevented epithelial-to-mesenchymal transition and activated autophagy; this was regulated through the interaction between autophagy-associated gene 5 (Atg5) and the mitogen-activated protein kinase pathway. In addition, the knockdown of NTF4 inhibited cell invasion, migration, proliferation and colony formation, and promoted cell cycle arrest. Treatment of the cells with the autophagy inhibitor chloroquine (CQ) rescued these functions and promoted cell invasion, migration, proliferation and colony formation. Finally, the knockdown of NTF4 inhibited the growth of subcutaneous xenografts in Balb/c-nu mice. In conclusion, these findings suggested that NTF4 may be a diagnostic marker associated with the overall survival and progression of patients with CRC. NTF4 was found to promote tumorigenesis and CRC development through autophagy regulation.

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Section: Discussionmentioning

confidence: 93%

Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy

et al. 2020

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“…Autophagy levels are very low under physiological conditions, but are up-regulated in response to stress, such as hypoxia [ 28 , 29 ]. Previous studies have demonstrated that autophagy could regulate cell proliferation, migration and angiogenesis [ 30 , 31 ]. Based on our present study, it is sure that miR-195 could regulate autophagy process under hypoxic conditions.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-195 regulates proliferation, migration, angiogenesis and autophagy of endothelial progenitor cells by targeting GABARAPL1

Zhang

Yang

2016

Bioscience Reports

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Deep vein thrombosis (DVT) is a common type of venous thrombosis. Successful resolution of DVT-related thrombi is important in the treatment of DVT. Endothelial progenitor cells (EPCs) have emerged as a promising therapeutic choice for DVT-related thrombus resolution; however, the clinical application of EPCs faces many challenges. In the present study, the expression of miR-582, miR-195 and miR-532 under hypoxic or normoxic conditions was measured using quantitative real-time PCR analysis (qRT-PCR) and the results showed that the increased fold of miR-195 was highest in human EPCs (hEPCs) under hypoxic conditions. Then the role and regulating mechanism of miR-195 in improving the function of EPCs was investigated. To investigate the effect of miR-195 inhibition on the autophagy of hEPCs, the expression of the autophagy-related genes LC3B and beclin1 was examined using western blotting, and the formation of autophagosomes was observed using TEM. The results indicated that the inhibition of miR-195 expression could promote autophagy of hEPCs. In addition, we investigated the role of miR-195 on the proliferation, migration and angiogenesis of hEPCs under hypoxia. The results revealed that miR-195 inhibition promotes cell proliferation, migration and angiogenesis of hEPCs under hypoxia. Furthermore, GABA type A receptor associated protein like 1 (GABARAPL1) was identified as a directed target of miR-195 and GABARAPL1 silencing could decrease the effect of miR-195 knockdown on cell proliferation, migration, angiogenesis and autophagy of hEPCs under hypoxia. Together, these results indicate that miR-195 regulates cell proliferation, migration, angiogenesis and autophagy of hEPCs by targeting GABARAPL1.

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“…Inhibition of the chaperone protein HSP90 (heat-shock protein-90) also induces K48-linked poly-ubiquitination and degradation of BECN1, suppressing TLR-mediated autophagy ( Xu et al, 2011 ). Ring family ubiquitin ligase RNF216 (ring-finger protein-216) is another protein which suppresses autophagy by inducing K48-linked poly-ubiquitination and degradation of BECN1 in TLR-stimulated macrophages and colon cancer ( Xu et al, 2014 ; Wang et al, 2016 ). Although the ubiquitin ligase NEDD4 (neural precursor cell expressed developmentally down-regulated protein 4) was shown to inhibit autophagy by K11-linked poly-ubiquitination and degradation of BECN1, recent evidences suggest a pro-autophagic role for this protein ( Platta et al, 2012 ; Pei et al, 2017 ; Sun et al, 2017 ).…”

Section: Other Ptms Regulating Becn1mentioning

confidence: 99%

Beclin 1 Phosphorylation – at the Center of Autophagy Regulation

Menon

Dhamija

2018

Front. Cell Dev. Biol.

282

187

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Autophagy is a tightly regulated catabolic process wherein cells under stress sequester cytosolic constituents like damaged proteins and organelles in double-membrane vesicles called autophagosomes. The autophagosomes degrade their cargo by lysosomal proteolysis generating raw materials for the biosynthesis of vital macromolecules. One of the initial steps in the assembly of autophagosomes from pre-autophagic structures is the recruitment and activation of the class III phosphatidylinositol 3-kinase complex consisting of Beclin 1 (BECN1), VPS34, VPS15, and ATG14 proteins. Several pieces of evidence indicate that the phosphorylation and ubiquitination of BECN1 at an array of residues fine-tune the responses to diverse autophagy modulating stimuli and helps in maintaining the balance between pro-survival autophagy and pro-apoptotic responses. In this mini-review, we will discuss the importance of distinct BECN1 phosphorylation events, the diverse signaling pathways and kinases involved and their role in the regulation of autophagy.

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RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy

Cited by 35 publications

References 35 publications

Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy

Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy

MicroRNA-195 regulates proliferation, migration, angiogenesis and autophagy of endothelial progenitor cells by targeting GABARAPL1

Beclin 1 Phosphorylation – at the Center of Autophagy Regulation

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