Mutual regulation between OGT and XIAP to control colon cancer cell growth and invasion

Seo, Hyeon Gyu; Kim, Han Byeol; Yoon, Ji Young; Kweon, Tae Hyun; Park, Yun Soo; Kang, Jingu; Jung, Jin Seung; Son, SeongJin; Yi, Eugene C.; Lee, Tae Ho; Yang, Won Ho; Cho, Jin Won

doi:10.1038/s41419-020-02999-5

Cited by 31 publications

(19 citation statements)

References 53 publications

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“…In this study, we identified the aberrantly elevated expression of OGT and OGA as a consequence of KU60019 treatment in SKOV3 cells. These results are consistent with studies on colon cancer ( 31 ), intestinal tumorigenesis ( 32 ), and other types of tumorigeneses. Significant cell death was also found in SKOV3 cells after ATM inhibition, indicating a potential correlation between cell viability and energy metabolism-related genes.…”

Section: Discussionsupporting

confidence: 92%

Blocking ATM Attenuates SKOV3 Cell Proliferation and Migration by Disturbing OGT/OGA Expression via hsa-miR-542-5p

Wang

Yu²,

Yan³

et al. 2022

Front. Oncol.

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Blocking ataxia telangiectasia mutated (ATM), a crucial player in DNA repair responses, has been proposed as a promising strategy in anti-cancer therapy. Most previous studies have focused on DNA damage response-related pathways after administration of ATM inhibitors. However, ATM inhibition could potentially influence a wide range of changes in gene expression, which remain poorly defined. Here, we report that administration of the ATM inhibitor KU60019 led to impaired migration and enhanced apoptosis in the ovarian cancer cell line SKOV3, accompanied by abnormally elevated O-GlcNAc transferase and O-GlcNAcase expression levels. In addition, KU60019 treatment significantly suppressed expression of hsa-miR-542-5p in SKOV3 cells. Up-regulation of hsa-miR-542-5p expression inhibited increases in OGT and OGA level, and reversed the effects of ATM inhibition on apoptosis and migration in SKOV3 cells. Finally, we found aberrant expression of OGT and OGA to be associated with ovarian cancer patient survival. Taken together, our results suggest that ATM inhibition may promote SKOV3 cell apoptosis via suppressing hsa-miR-542-5p and elevating OGT and OGA expression, providing new insights into the application of ATM inhibitors in cancer immunotherapy.

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Section: Discussionsupporting

confidence: 92%

Blocking ATM Attenuates SKOV3 Cell Proliferation and Migration by Disturbing OGT/OGA Expression via hsa-miR-542-5p

Wang

Yu²,

Yan³

et al. 2022

Front. Oncol.

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“…A number of E3 UB ligases have been reported to interact with OGT and regulate its activity in the cell. In addition to histone methyltransferase, LSD2 and Ring E3 XIAP that have been shown to ubiquitinate OGT in reconstituted ubiquitination assays in vitro and in the cell [ 10 , 11 ]. β-TrCP, a substrate adaptor of the Skp1–Cullin–F-box-protein (SCF) E3, was found to destabilize OGT in the cell, although the ubiquitination of OGT catalyzed by the SCF complex bridged by β-TrCP is yet to be confirmed [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…This would enable UB transfer from LSD2 to OGT and induce the degradation of OGT [ 10 ]. Recently, Ring E3 XIAP was found to recognize OGT as a ubiquitination target and signal its degradation by the proteasome [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Regulation of O-Linked N-Acetyl Glucosamine Transferase (OGT) through E6 Stimulation of the Ubiquitin Ligase Activity of E6AP

Peng

Liu

Jia

et al. 2021

IJMS

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Glycosyltransferase OGT catalyzes the conjugation of O-linked β-D-N-acetylglucosamine (O-GlcNAc) to Ser and Thr residues of the cellular proteins and regulates many key processes in the cell. Here, we report the identification of OGT as a ubiquitination target of HECT-type E3 ubiquitin (UB) ligase E6AP, whose overexpression in HEK293 cells would induce the degradation of OGT. We also found that the expression of E6AP in HeLa cells with the endogenous expression of the E6 protein of the human papillomavirus (HPV) would accelerate OGT degradation by the proteasome and suppress O-GlcNAc modification of OGT substrates in the cell. Overall, our study establishes a new mechanism of OGT regulation by the ubiquitin–proteasome system (UPS) that mediates the crosstalk between protein ubiquitination and O-GlcNAcylation pathways underlying diverse cellular processes.

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“…Because of their outstanding capacity to regulate cell death along with their high expression in many types of tumor cells, IAPs may be a new target for cancer therapy in the future. Increasing evidence suggests that suppression of XIAP can inhibit tumor growth in gastric cancer [ 38 ], prostate cancer [ 39 ], colon cancer [ 40 ], and HCC [ 41 ]. In this study, XIAP could bind with miR-212-3p and mechanistically antagonize the inhibitory effect of miR-212-3p on carcinogenesis, indicating that XIAP is likely to be associated with tumorigenesis and enhance the malignant behavior of HCC cells, which is consistent with the results of 41 [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Down-regulated HSA_circ_0003528 inhibits hepatocellular carcinoma aggressiveness via the miR-212-3p/XIAP axis

Liu

Sun

2022

Bioengineered

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Hepatocellular carcinoma (HCC) is characterized by a high mortality rate. Dysregulated circular RNAs (circRNAs) play a vital role in HCC. We aimed to study the role of circ_0003528 in HCC and its fundamental molecular mechanisms. HSA_circ_0003528 was identified through bioinformatics dataset analysis. The binding sites between mRNA and miRNA were predicted using online bioinformatics tools. The interaction between miR-212-3p and X-linked inhibitor of apoptosis protein ( XIAP ) or circ_0003528 was confirmed through the luciferase reporter assay. RT-qPCR and western blot assays were used to analyze the expression of all miRNAs/mRNAs and proteins. Cellular functions were evaluated using the MTT and TUNEL assays. A xenograft model was established to evaluate the function of circ_0003528 in vivo . Circ_0003528 was dramatically overexpressed in HepG2 and HUH7 cells. However, knockdown of circ_0003528 suppressed the aggressiveness of HCC cells and tumor growth both in vitro and in vivo . Furthermore, binding of miR-212-3p to circ_0003528 and XIAP was verified. Downregulation of miR-212-3p abrogated the effects of si-circ_0003528 on cell viability and apoptosis, and upregulation of XIAP antagonized the functions of the miR-212-3p mimic in HCC cells. circ_0003528 contributes to the development of HCC in vitro and in vivo via the miR-212-3p/ XIAP axis. Hence, circ_0003528 knockdown may be a potential therapeutic strategy for HCC treatment.

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Mutual regulation between OGT and XIAP to control colon cancer cell growth and invasion

Cited by 31 publications

References 53 publications

Blocking ATM Attenuates SKOV3 Cell Proliferation and Migration by Disturbing OGT/OGA Expression via hsa-miR-542-5p

Blocking ATM Attenuates SKOV3 Cell Proliferation and Migration by Disturbing OGT/OGA Expression via hsa-miR-542-5p

Regulation of O-Linked N-Acetyl Glucosamine Transferase (OGT) through E6 Stimulation of the Ubiquitin Ligase Activity of E6AP

Down-regulated HSA_circ_0003528 inhibits hepatocellular carcinoma aggressiveness via the miR-212-3p/XIAP axis

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