Jab1/Cops5: a promising target for cancer diagnosis and therapy

Yuan, Chunjue; Wang, Dong; Liu, Guohong; Pan, Yunbao

doi:10.1007/s10147-021-01933-9

Cited by 16 publications

(11 citation statements)

References 65 publications

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“…Previous studies have shown that the expression level of Jab1 is elevated in many tumors, including NPC (16), which is consistent with the findings of our study. We found that Jab1 is elevated in the tumor cell-enriched regions compared with the normal epithelial-enriched regions.…”

Section: Discussionsupporting

confidence: 93%

“…One molecular mechanism leading to NPC tumorigenesis involves the fifth component of the COP9 signalosome complex (Csn5, COPS5 or Jab1). Jab1 acts as a modulator of intracellular signaling and affects cellular proliferation, apoptosis, and DNA damage response by interacting with several key regulatory proteins and affecting these proteins' subcellular localization, degradation, phosphorylation, and deneddylation (16). Jab1 has been reported to be associated with cuproptosis related genes.…”

Section: Introductionmentioning

confidence: 99%

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Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma

Wang

Liu

et al. 2022

Front. Immunol.

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BackgroundNasopharyngeal carcinoma (NPC) is the most common subcategory of head and neck squamous cell carcinoma (HNSCC). This study focused on the roles of cuproptosis related genes and Jab1 in the tumor microenvironment of NPC and HNSCC.MethodsDifferential expression analysis of Jab1 and cuproptosis related genes in tumor cell enriched region (PanCK-expressing) and immune cell enriched region (CD45-expressing) of NPC microenvironment were performed by packages of R software. Survival analysis was performed using the survival and survminer packages. Corrplot package was used for correlation analysis. ConsensusClusterPlus package was used for cluster clustering among different regions of NPC, and functional enrichment analysis was performed using GSVA, GSEABase, clusterProfiler, org.Hs.eg.db and enrichplot packages. The pRRophetic package was used to predict drug sensitivity in NPC and HNSCC.ResultsRelationships exist between cuproptosis related genes and Jab1 in the NPC microenvironment. The expression of cuproptosis related genes and Jab1 differed between tumor cell enriched region and immune cell enriched region. AKT inhibitor VIII, Doxorubicin, Bleomycin and Etoposide showed higher sensitivity to tumor cell than immune cell. In the high Jab1 group, higher expression of ATP7A, DBT, DLD and LIAS were associated with better prognosis of HNSCC patients. In contrast, in the low Jab1 group, higher expression of these genes is associated with worse prognosis of HNSCC patients.ConclusionsPrognostic cuproptosis related genes and Jab1 provided a basis for targeted therapy and drug development.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma

Wang

Liu

et al. 2022

Front. Immunol.

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“…A study combining expression analysis in patient biopsies with functional in vitro and in vivo investigations demonstrated that let-7d regulates cell growth and invasion in breast cancer, and also inhibits Jab1 (Jun activation domain-binding protein 1) protein expression [ 57 ]. Jab1 is a component of the COP9 signalosome protein complex that regulates fundamental cellular processes linked to the ubiquitin–proteasome system [ 58 ]. It acts as a docking interface for protein kinases, thereby affecting numerous signaling pathways relevant to tumor progression, including p53, p27 AP-1 and Smad proteins active in TGF-β1 signaling [ 59 , 60 , 61 ].…”

Section: Let-7d and Breast Cancermentioning

confidence: 99%

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

Santis¹,

Götte²

2021

IJMS

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microRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Let-7d is a microRNA of the conserved let-7 family that is dysregulated in female malignancies including breast cancer, ovarian cancer, endometrial cancer, and cervical cancer. Moreover, a dysregulation is observed in endometriosis and pregnancy-associated diseases such as preeclampsia and fetal growth restriction. Let-7d expression is regulated by cytokines and steroids, involving transcriptional regulation by OCT4, MYC and p53, as well as posttranscriptional regulation via LIN28 and ADAR. By downregulating a wide range of relevant mRNA targets, let-7d affects cellular processes that drive disease progression such as cell proliferation, apoptosis (resistance), angiogenesis and immune cell function. In an oncological context, let-7d has a tumor-suppressive function, although some of its functions are context-dependent. Notably, its expression is associated with improved therapeutic responses to chemotherapy in breast and ovarian cancer. Studies in mouse models have furthermore revealed important roles in uterine development and function, with implications for obstetric diseases. Apart from a possible utility as a diagnostic blood-based biomarker, pharmacological modulation of let-7d emerges as a promising therapeutic concept in a variety of female disease conditions.

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“…Several reports have explained the association of Jab1/p27 inverse correlation with the phytocompound-mediated apoptosis induction in cancer cells [37][38][39][40]. Jab1 executes its biological role by promoting the degradation of several tumor suppressor genes including p27 and p53 via translocating them from the nucleus to cytoplasm [41,42].…”

Section: Discussionmentioning

confidence: 99%

A Novel Approach to Unraveling the Apoptotic Potential of Rutin (Bioflavonoid) via Targeting Jab1 in Cervical Cancer Cells

et al. 2021

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Rutin has been well recognized for possessing numerous pharmacological and biological activities in several human cancer cells. This research has addressed the inhibitory potential of rutin against the Jab1 oncogene in SiHa cancer cells, which is known to inactivate various tumor suppressor proteins including p53 and p27. Further, the inhibitory efficacy of rutin via Jab1 expression modulation in cervical cancer has not been yet elucidated. Hence, we hypothesized that rutin could exhibit strong inhibitory efficacy against Jab1 and, thereby, induce significant growth arrest in SiHa cancer cells in a dose-dependent manner. In our study, the cytotoxic efficacy of rutin on the proliferation of a cervical cancer cell line (SiHa) was exhibited using MTT and LDH assays. The correlation between rutin and Jab1 mRNA expression was assessed by RT-PCR analysis and the associated events (a mechanism) with this downregulation were then explored via performing ROS assay, DAPI analysis, and expression analysis of apoptosis-associated signaling molecules such as Bax, Bcl-2, and Caspase-3 and -9 using qRT-PCR analysis. Results exhibit that rutin produces anticancer effects via inducing modulation in the expression of oncogenes as well as tumor suppressor genes. Further apoptosis induction, caspase activation, and ROS generation in rutin-treated SiHa cancer cells explain the cascade of events associated with Jab1 downregulation in SiHa cancer cells. Additionally, apoptosis induction was further confirmed by the FITC-Annexin V/PI double staining method. Altogether, our research supports the feasibility of developing rutin as one of the potent drug candidates in cervical cancer management via targeting one such crucial oncogene associated with cervical cancer progression.

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Jab1/Cops5: a promising target for cancer diagnosis and therapy

Cited by 16 publications

References 65 publications

Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma

Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

A Novel Approach to Unraveling the Apoptotic Potential of Rutin (Bioflavonoid) via Targeting Jab1 in Cervical Cancer Cells

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