Nuclear receptors in oral cancer-Emerging players in tumorigenesis

Gangwar, Shailendra Kumar; Kumar, Aviral; Jose, Sandra; Alqahtani, Mohammed S.; Abbas, Mohamed; Sethi, Gautam; Kunnumakkara, Ajaikumar B.

doi:10.1016/j.canlet.2022.215666

Cited by 17 publications

(16 citation statements)

References 255 publications

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“…NRs are divided into three categories depending on their binding with the ligands: endocrine, adopted, and orphan NRs. Most of the tissues in the body express numerous types of NRs that are sensitive to diverse types of ligands, and they function in the control of the expression of target genes required in tumor formation and suppression [ 29 ]. NRs play a crucial role in cellular activities as well as in a diverse range of pathological diseases, including cancer [ 21 , 30 , 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Nuclear Receptors in Lung Cancer—Novel Therapeutic Prospects

et al. 2022

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Lung cancer, the second most commonly diagnosed cancer, is the major cause of fatalities worldwide for both men and women, with an estimated 2.2 million new incidences and 1.8 million deaths, according to GLOBOCON 2020. Although various risk factors for lung cancer pathogenesis have been reported, controlling smoking alone has a significant value as a preventive measure. In spite of decades of extensive research, mechanistic cues and targets need to be profoundly explored to develop potential diagnostics, treatments, and reliable therapies for this disease. Nuclear receptors (NRs) function as transcription factors that control diverse biological processes such as cell growth, differentiation, development, and metabolism. The aberrant expression of NRs has been involved in a variety of disorders, including cancer. Deregulation of distinct NRs in lung cancer has been associated with numerous events, including mutations, epigenetic modifications, and different signaling cascades. Substantial efforts have been made to develop several small molecules as agonists or antagonists directed to target specific NRs for inhibiting tumor cell growth, migration, and invasion and inducing apoptosis in lung cancer, which makes NRs promising candidates for reliable lung cancer therapeutics. The current work focuses on the importance of various NRs in the development and progression of lung cancer and highlights the different small molecules (e.g., agonist or antagonist) that influence NR expression, with the goal of establishing them as viable therapeutics to combat lung cancer.

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Section: Introductionmentioning

confidence: 99%

Targeting Nuclear Receptors in Lung Cancer—Novel Therapeutic Prospects

et al. 2022

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“…Moreover, various (patho)biological effects of nuclear receptors in the absence (‘ligand-independent’) and/or presence of their ligands (‘ligand-dependent’) have been reported [ 15 , 16 ]. The mechanistic details of these activities are not fully understood and thereby increase the complexity of nuclear receptor research and interpretation of observations [ 12 , 14 , 17 ]. Due to this complexity, we need to refer the reader to some comprehensive reviews for more details [ 12 , 14 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanistic details of these activities are not fully understood and thereby increase the complexity of nuclear receptor research and interpretation of observations [ 12 , 14 , 17 ]. Due to this complexity, we need to refer the reader to some comprehensive reviews for more details [ 12 , 14 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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The Vitamin D Receptor–BIM Axis Overcomes Cisplatin Resistance in Head and Neck Cancer

Khamis

Gül

Wandrey

et al. 2022

Cancers

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Treatment success of head and neck squamous cell carcinoma (HNSCC) is often hindered by cisplatin resistance. As inherent and acquired therapy resistance counteracts improvement in long-term survival, novel multi-targeting strategies triggering cancer cell apoptosis are urgently required. Here, we identify the vitamin D receptor (VDR) as being significantly overexpressed in tumors of HNSCC patients (n = 604; p = 0.0059), correlating with tumor differentiation (p = 0.0002), HPV status (p = 0.00026), and perineural invasion (p = 0.0087). The VDR, a member of the nuclear receptor superfamily, is activated by its ligand vitamin D (VitD) and analogs, triggering multiple cellular responses. As we found that the VDR was also upregulated in our cisplatin-resistant HNSCC models, we investigated its effect on overcoming cisplatin resistance. We discovered that VitD/cisplatin combinations synergistically killed even cisplatin-resistant cells at clinically achievable levels. Similar results were obtained for the clinically used VitD analog Maxacalcitol. Moreover, VitD/cisplatin combinations inhibited tumor cell migration by E-cadherin upregulation. Signaling pathway analyses revealed that VitD co-treatments triggered cancer cell death by increasing the expression of the pro-apoptotic BCL-2 family protein BIM. BIM’s pro-apoptotic activity in HNSCC cells was confirmed by ectopic overexpression studies. Importantly, BIM expression is positively associated with HNSCC patients’ (n = 539) prognosis, as high expression correlated with improved survival (p = 0.0111), improved therapy response (p = 0.0026), and remission (p = 0.004). Collectively, by identifying, for the first time, the VDR/BIM axis, we here provide a molecular rationale for the reported anti-cancer activity of VitD/analogs in combination therapies. Our data also suggest its exploitation as a potential strategy to overcome cisplatin resistance in HNSCC and other malignancies by inducing additional pro-apoptotic pathways.

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“…Oral cancer is a widely prevalent disease in the world, which is one of intractable issues for model society [ 1 , 2 ]. At present, surgical operation, chemotherapy, and radiotherapy are major therapeutic strategies for oral cancer.…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential miRNA-mRNA Regulatory Network in the Development of Oral Cancer

Yang

Xin

2022

Disease Markers

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Background. Oral cancer is a difficult question in modern medical system, and there are few effective strategies to completely heal these diseases. This research investigated the miRNA-mRNA network in oral cancer development via bioinformatics excavation. Methods. GSE28100 and GSE23558 in the GEO database were selected for bioinformatics analysis. The datasets were analyzed with GEO2R to obtain the related matrix files. The hot plot and heatmap of the matrix files were drawn with R language. The MiRDIP database was applied to predict and screen the targets of miRNAs. The DEGs in the matrix files were analyzed with the DAVID database and visualized with R language for enrichment analysis. The PPI-network of the DEGs was established with the STRING database and Cytoscape. Besides, the miRNA-mRNA was visualized by Cytoscape. Results. 35 genes were identified as the DEGs in GES28100. 1651 genes were identified as the DEGs in GSE23558. 143 common genes in the targets of miRNAs in GSE28100 and the DEGs in GSE the targets of DEGs in GES28100 and common genes were enriched in the PI3K/AKT pathway, MAPK pathway, etc. The DEGs in GSE28100 and GSE23558 were involved in the regulations of transcription from RNA polymerase II promoter and DNA transcription. The DEGs in GSE28100 and GSE23558 were established with the miRNA-mRNA network. Conclusion. This research identified miR-15b-5p, miR-199a-3p, miR-21-5p, miR-424-5p, and miR-454-3p as the biomarker of oral cancer and established the miRNA-mRNA network in oral progression.

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Nuclear receptors in oral cancer-Emerging players in tumorigenesis

Cited by 17 publications

References 255 publications

Targeting Nuclear Receptors in Lung Cancer—Novel Therapeutic Prospects

Targeting Nuclear Receptors in Lung Cancer—Novel Therapeutic Prospects

The Vitamin D Receptor–BIM Axis Overcomes Cisplatin Resistance in Head and Neck Cancer

Identification of Potential miRNA-mRNA Regulatory Network in the Development of Oral Cancer

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