Roles of E3 ubiquitin ligases in gastric cancer carcinogenesis and their effects on cisplatin resistance

Wang, Huizhen; Lu, Yida; Wang, Mingliang; Wu, Youliang; Wang, Xiaodong; Li, Yongxiang

doi:10.1007/s00109-020-02015-5

Cited by 17 publications

(15 citation statements)

References 175 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Being a P53-specific E3 ubiquitin ligase, MDM2 is a principal factor in P53 destruction (28). MDM2 has proved to play an essential role in cancer progression by inducing cell proliferation, invasion, and therapeutic resistance and inhibiting the apoptotic process, serving as a useful predictive marker for poor prognosis in various human cancers such as GC, breast cancer, hepatocellular carcinoma, and lung cancer (11,(29)(30)(31). MDM2 expression parameters are closely correlated with H. pylori infection and higher stages GC (29).…”

Section: Discussionmentioning

confidence: 99%

“…Glaucocalyxin A (GLA), an entkauranoid diterpene isolated from Rab-dosia japonica var., exhibits multiple pharmacological effects such as anticancer effect, induction of osteogenesis, suppression of inflammation, and prevention of myocardial infarction (2)(3)(4)(5)(6)(7)(8)(9). MDM2 and RNF6 are extensivelystudied oncoproteins in various malignancies, including GC (10)(11)(12)(13). Mdm2 is an oncogene mapped to chromosome 12q13-14, and the most critical function of MDM2 in cancers is to target the tumor suppressor P53 protein via proteasomal degradation or blockade of activity (10).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glaucocalyxin A Inhibits the Malignancies of Gastric Cancer Cells by Downregulating MDM2 and RNF6 via MiR-3658 and the SMG1-UPF mRNA Decay Pathway

Liu

Chen

Qi³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Gastric cancer (GC) ranks as the most common gastrointestinal cancer and is among the leading causes of cancer death worldwide. Glaucocalyxin A (GLA), an entkauranoid diterpene isolated from Rab-dosia japonica var., possesses various bioactivities. To date, the data on the effect of GLA on GC are still minimal, and the molecular mechanisms remain largely unknown. Herein, we found that GLA could significantly inhibit the proliferation, cell adhesion, and invasion of HGT-1, SNU-1, SNU-6, and NCI-N87 GC cells in a dose-dependent manner. GLA enhanced the apoptosis of the GC cells as evidenced by the increased caspase-3 activity and the elevated levels of cleaved caspase-3 and cleaved PARP in GC cells in the presence of GLA. We then showed that the downregulation of Murine Double Minute Clone 2 (MDM2) and Ring Finger Protein 6 (RNF6) by GLA was implicated in the GLA-induced inhibition of the GC cells. Furthermore, MDM2 and RNF6 were identified as the targets of miR-3658 that was downregulated in the GC cells and upregulated by GLA. Moreover, it was shown that miR-3658 was hypermethylated in the GC cells, and GLA could rescue the expression of miR-3658 via demethylation by abrogating EZH2-mediated epigenetic silencing. In addition to the miR-3658-MDM2/RNF6 regulatory axis, activation of the SMG1-UPF mRNA decay pathway contributed to the downregulation of MDM2 and RNF6 by GLA in the GC cells. The inhibitory effect of GLA on gastric cancer and the expression of MDM2 and RNF6 was also validated in in vivo study. Our findings suggest that has the therapeutic potential for GC by downregulating oncogenes via posttranscriptional regulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glaucocalyxin A Inhibits the Malignancies of Gastric Cancer Cells by Downregulating MDM2 and RNF6 via MiR-3658 and the SMG1-UPF mRNA Decay Pathway

Liu

Chen

Qi³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…When RNF180 was abnormally expressed, a variety of physical, chemical, and biological factors were affected, resulting in decreased gene expression or corresponding protein dysfunction. It has been confirmed that the inactivation of RNF180 is associated with apoptosis, tumor invasion and metastasis[ 14 , 15 ]. Downregulation of RNF180 gene expression was related to hypermethylation in the promoter region, and the methylated RNF180 gene played an important role in the occurrence, development, prognosis of GC and infection of H. pylori [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Droplet digital polymerase chain reaction assay for methylated ring finger protein 180 in gastric cancer

Guo¹,

Jiang²,

An³

2022

World J Gastrointest Oncol

View full text Add to dashboard Cite

BACKGROUND Gastric cancer (GC) is one of the most prevalent malignant tumors that endangers human health. Early diagnosis is essential for improving the prognosis and survival rate of GC patients. Ring finger protein 180 (RNF180) is involved in the regulation of cell differentiation, proliferation, apoptosis, and tumorigenesis, and aberrant hypermethylation of CpG islands in the promoter is strongly associated with the occurrence and development of GC. Thus, methylated RNF180 can be used as a potential biomarker for GC diagnosis. AIM To use droplet digital polymerase chain reaction (ddPCR) to quantify the methylation level of the RN180 gene. A reproducible ddPCR assay to detect methylated RNF180 from trace DNA was designed and optimized. METHODS The primer and probe were designed and selected, the conversion time of bisulfite was optimized, the ddPCR system was adjusted by primer concentration, amplification temperature and amplification cycles, and the detection limit of ddPCR was determined. RESULTS The best conversion time for blood DNA was 2 h 10 min, and that for plasma DNA was 2 h 10 min and 2 h 30 min. The results of ddPCR were better when the amplification temperature was 56 °C and the number of amplification cycles was 50. Primer concentrations showed little effect on the assay outcome. Therefore, the primer concentration could be adjusted according to the reaction system and DNA input. The assay required at least 0.1 ng of input DNA. CONCLUSION In summary, a ddPCR assay was established to detect methylated RNF180, which is expected to be a new diagnostic biomarker for GC.

show abstract

“…The E3 ligase plays a crucial role in the process of protein ubiquitination by transferring ubiquitin to the lysine residues of the substrates with the cooperation of the E1 and E2 enzymes. Additionally, the E3 ligase is involved in cellular non-degradable functions such as DNA repair, metabolism, and protein complex assembly ( 5 ). Dysfunction of the E3 ligase caused by its mutation regulates many signaling pathways, promoting the development of cancer ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, the E3 ligase is involved in cellular non-degradable functions such as DNA repair, metabolism, and protein complex assembly ( 5 ). Dysfunction of the E3 ligase caused by its mutation regulates many signaling pathways, promoting the development of cancer ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy

Chen

Jiang²,

Zhao³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

FBXW7 (F-box and WD repeat domain containing 7) is a critical subunit of the Skp1-Cullin1-F-box protein (SCF), acting as an E3 ubiquitin ligase by ubiquitinating targeted protein. Through degradation of its substrates, FBXW7 plays a pivotal role in drug resistance in tumor cells and shows the potential to rescue the sensitivity of cancer cells to drug treatment. This explains why patients with higher FBXW7 levels exhibit higher survival times and more favorable prognosis. Furthermore, FBXW7 has been demonstrated to enhance the efficacy of immunotherapy by targeting the degradation of specific proteins, as compared to the inactivated form of FBXW7. Additionally, other F-box proteins have also shown the ability to conquer drug resistance in certain cancers. Overall, this review aims to explore the function of FBXW7 and its specific effects on drug resistance in cancer cells.

show abstract

Roles of E3 ubiquitin ligases in gastric cancer carcinogenesis and their effects on cisplatin resistance

Cited by 17 publications

References 175 publications

Glaucocalyxin A Inhibits the Malignancies of Gastric Cancer Cells by Downregulating MDM2 and RNF6 via MiR-3658 and the SMG1-UPF mRNA Decay Pathway

Glaucocalyxin A Inhibits the Malignancies of Gastric Cancer Cells by Downregulating MDM2 and RNF6 via MiR-3658 and the SMG1-UPF mRNA Decay Pathway

Droplet digital polymerase chain reaction assay for methylated ring finger protein 180 in gastric cancer

FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy

Contact Info

Product

Resources

About