UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance

Huang, Yumei; Yang, Xuezhou; Lu, Yutong; Zhao, Ye; Meng, Rui; Zhang, Sheng; Dong, Xiaorong; Xu, Shuangbing; Wu, Gang

doi:10.1038/s41418-020-00616-8

Cited by 51 publications

(46 citation statements)

References 32 publications

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“…The dysregulation of UBE2O and its clinical significance has been previously reported in several types of human cancers. UBE2O is highly expressed in lung cancer tissues, and its overexpression predicts poor prognosis 19 . The overexpression of UBE2O is confirmed in breast cancer tissues, and UBE2O expression is higher in patients with a poor prognosis and an increased risk of metastasis 18 .…”

Section: Discussionmentioning

confidence: 99%

“…We randomly selected five high-power fields of view for each section. The intensity of staining was scored as 0 (negative), 1 (weak), 2 (moderate), and 3 (strong), and we scored the percentage of UBE2O positive tumor cells as 1 (0-25%), 2 (26-50%), 3 (51-75%), and 4 (75-100%) 19 . The IHC score was equal to the intensity score multiplied by the positive rate score.…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies report the oncogenic or tumorsuppressive role of UBE2O in human cancers [14][15][16][17][18][19]. For example, UBE2O mediates the multi-monoubiquitination of BRCA1-associated protein 1 (BAP1) and subsequently reduces its cytoplasmic retention [15].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

“…UBE2O targets c-Maf for ubiquitination and degradation to repress the tumor growth of myeloma 17 . Mxi1 is identified as a substrate of UBE2O and mediates the tumor-promoting role of UBE2O in lung cancer 19 . AMP-activated protein kinase α2 (AMPKα2) is a classical target protein of UBE2O in skeletal muscle and human cancers 16 , 18 , 20 .…”

Section: Introductionmentioning

confidence: 99%

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UBE2O promotes hepatocellular carcinoma cell proliferation and invasion by regulating the AMPKα2/mTOR pathway

Shi¹,

Liu²,

Lu³

et al. 2021

Int. J. Med. Sci.

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The ubiquitin-conjugating enzyme (E2) is a critical component of the ubiquitin-proteasome system and regulates hepatocarcinogenesis by controlling protein degradation. Ubiquitin-conjugating enzyme E2 O (UBE2O), a member of the E2 family, functions as an oncogene in human cancers. Nevertheless, the role of UBE2O in hepatocellular carcinoma (HCC) remains unknown yet. Here, we demonstrated that the UBE2O level was markedly upregulated in HCC compared with adjacent noncancerous tissues. UBE2O overexpression was also confirmed in HCC cell lines. UBE2O overexpression was prominently associated with advanced tumor stage, high tumor grade, venous infiltration, and reduced HCC patients' survivals. UBE2O knockdown inhibited the migration, invasion, and proliferation of HCCLM3 cells. UBE2O overexpression enhanced the proliferation and mobility of Huh7 cells. Mechanistically, UBE2O mediated the ubiquitination and degradation of AMP-activated protein kinase α2 (AMPKα2) in HCC cells. UBE2O silencing prominently increased AMPKα2 level and reduced phosphorylated mechanistic target of rapamycin kinase (p-mTOR), MYC, Cyclin D1, HIF1α, and SREBP1 levels in HCCLM3 cells. UBE2O depletion markedly activated the AMPKα2/mTOR pathway in Huh7 cells. Moreover, AMPKα2 silencing reversed UBE2O downregulation-induced mTOR pathway inactivation. Rapamycin, an inhibitor of mTOR, remarkably abolished UBE2O-induced mTOR phosphorylation and HCC cell proliferation and mobility. To conclude, UBE2O was highly expressed in HCC and its overexpression conferred to the poor clinical outcomes of patients. UBE2O contributed to the malignant behaviors of HCC cells, including cell proliferation, migration, and invasion, by reducing AMPKα2 stability and activating the mTOR pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ivyspring International Publishermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

UBE2O promotes hepatocellular carcinoma cell proliferation and invasion by regulating the AMPKα2/mTOR pathway

Shi¹,

Liu²,

Lu³

et al. 2021

Int. J. Med. Sci.

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“…Deregulation of UBE2O has been associated with several human diseases, especially cancers. UBE2O could mediate Mxi1 ubiquitination and then promote lung cancer progression and radioresistance 25 . It has been reported that UBE2O could decrease the stability of MLL in a polyubiquitination-dependent manner, which results in aggressive leukaemia 26 .…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA HCG18 promotes malignant phenotypes of breast cancer (BC) cells by HCG18/miR-103a-3p/UBE2O/mTORC1/HIF-1α positive feedback loop

Liu

Qiao

Zhu

et al. 2021

Preprint

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Background: In recent years, a growing number of studies have reported that long non-coding RNAs (LncRNAs) play crucial roles in breast cancer (BC) progression and metastasis. Another study group of our research center reported that LncRNA HCG18 was one of the 30 upregulated lncRNAs in BC tissues related to normal tissues in TCGA database. However, the exactly biological roles of HCG18 in BC remains unclear. Method: qRT-PCR was used to detect the expression profile of HCG18 in BC tissues and cell lines. In vitro assays were used to evaluate the pro-tumor function of HCG18 in BC cells. Animal study were used to explore the role of HCG18 in vivo. Bioinformatic analysis, dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and Chromatin Immunoprecipitation (ChIP) assays were used to investigate the regulatory relationship of HCG18, miR-103a-3p, UBE2O in BC. Results: HCG18 was upregulated in BC tissues and cells, and BC patients with high HCG18 expression tended to have poor prognosis. HCG18 could promote BC cells proliferation, invasion and provided BC cells with tumor stemness properties (CSPs) in vitro and facilitate tumor growth and lung metastasis in vivo. In terms of mechanism, HCG18 functioned as a miRNA sponge which positively regulated the expression of Ubiquitin-conjugating enzyme E2O (UBE2O) by sponging miR-103a-3p and our previous research achievement have already verified UBE2O could promote malignant phenotypes of BC cells through UBE2O/AMPKα2/mTORC1 axis. Furthermore, as a downstream target of HCG18/miR-103a-3p/UBE2O/mTORC1 axis, HIF-1α transcriptionally promoted HCG18 expression and then formed a positive feedback loop in BC. Conclusion: HCG18 played an oncogenic role in BC and it might serve as a prognostic biomarker and a potential therapeutic target for BC treatment.

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The RNA interactome in the Hallmarks of Cancer

Gabryelska

Conn

2023

WIREs RNA

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Ribonucleic acid (RNA) molecules are indispensable for cellular homeostasis in healthy and malignant cells. However, the functions of RNA extend well beyond that of a protein‐coding template. Rather, both coding and non‐coding RNA molecules function through critical interactions with a plethora of cellular molecules, including other RNAs, DNA, and proteins. Deconvoluting this RNA interactome, including the interacting partners, the nature of the interaction, and dynamic changes of these interactions in malignancies has yielded fundamental advances in knowledge and are emerging as a novel therapeutic strategy in cancer. Here, we present an RNA‐centric review of recent advances in the field of RNA–RNA, RNA–protein, and RNA–DNA interactomic network analysis and their impact across the Hallmarks of Cancer.This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes

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UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance

Cited by 51 publications

References 32 publications

UBE2O promotes hepatocellular carcinoma cell proliferation and invasion by regulating the AMPKα2/mTOR pathway

UBE2O promotes hepatocellular carcinoma cell proliferation and invasion by regulating the AMPKα2/mTOR pathway

Long non-coding RNA HCG18 promotes malignant phenotypes of breast cancer (BC) cells by HCG18/miR-103a-3p/UBE2O/mTORC1/HIF-1α positive feedback loop

The RNA interactome in the Hallmarks of Cancer

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