GLI-1 polymorphisms of Hedgehog pathway as novel risk and prognostic biomarkers in melanoma patients

Dunjic, Marija; Lukić, Nikola; Djordjevic, Boban; Uzelac, Bojana; Ostojic, N.; Šupić, Gordana

doi:10.1097/cmr.0000000000000789

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…Even though phenotypic characteristics have been broadly described, the genetic structure of the population has rarely been highlighted, particularly in the quest to establish correlations between prevalence and geographic distribution [ 53 ]. Analyses of the rs357564 variant have been performed in several types of cancer and clinical conditions [ 54 , 55 , 56 , 57 ]. Most of the reports on rs357564, as well as the rest of the variants proposed in this investigation, have been related to BCC.…”

Section: Discussionmentioning

confidence: 99%

PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

Zambrano-Román,

Padilla-Gutiérrez,

Valle

et al. 2024

Biology

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Background: Skin cancer is one of the most frequent types of cancer, and cutaneous squamous cell carcinoma (cSCC) constitutes 20% of non-melanoma skin cancer (NMSC) cases. PTCH1, a tumor suppressor gene involved in the Sonic hedgehog signaling pathway, plays a crucial role in neoplastic processes. Methods: An analytical cross-sectional study, encompassing 211 cSCC patients and 290 individuals in a control group (CG), was performed. A subgroup of samples was considered for the relative expression analysis, and the results were obtained using quantitative real-time PCR (qPCR) with TaqMan® probes. The functional, splicing, and disease-causing effects of the proposed variants were explored via bioinformatics. Results: cSCC was predominant in men, especially in sun-exposed areas such as the head and neck. No statistically significant differences were found regarding the rs357564, rs2236405, rs2297086, and rs41313327 variants of PTCH1, or in the risk of cSCC, nor in the mRNA expression between the cSCC group and CG. A functional effect of rs357564 and a disease-causing relation to rs41313327 was identified. Conclusion: The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants.

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Section: Discussionmentioning

confidence: 99%

PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

Zambrano-Román,

Padilla-Gutiérrez,

Valle

et al. 2024

Biology

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“…Combined inhibition of the JAK2-STAT3 and Hedgehog pathways attenuates stemness and metastasis of breast cancer [ 36 ]. GLI1 inhibition facilitates multiple therapeutic approaches in distinctive cancer types [ 37 – 39 ]. GLI1 is also essential for stemness-related malignancy in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenine-mediated aberrant activation of the lncRNA SOX2OT-GLI1 loop promotes non-small-cell lung cancer stemness

et al. 2023

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Despite the advent of precision medicine and immunotherapy, mortality due to lung cancer remains high. The sonic hedgehog (SHH) cascade and its key terminal factor, glioma-associated oncogene homolog 1 (GLI1), play a pivotal role in the stemness and drug resistance of lung cancer. Here, we investigated the molecular mechanism of non-canonical aberrant GLI1 upregulation. The SHH cascade was upregulated in stem spheres and chemo-resistant lung cancer cells and was accountable for drug resistance against multiple chemotherapy regimens. GLI1 and the long non-coding RNA SOX2OT were positively regulated, and the GLI1-SOX2OT loop mediated the proliferation of parental and stem-like lung cancer cells. Further mechanistic investigation revealed that SOX2OT facilitated METTL3/14/IGF2BP2-mediated m6A modification and stabilization of the GLI1 mRNA. Additionally, SOX2OT upregulated METTL3/14/IGF2BP2 by sponging miR-186-5p. Functional analysis corroborated that GLI1 acted as a downstream target of METTL3/14/IGF2BP2, and GLI1 silencing could block the oncogenicity of lung cancer stem-like cells. Pharmacological inhibition of the loop remarkably inhibited the oncogenesis of lung cancer cells in vivo. Compared with paired adjacent normal tissues, lung cancer specimens exhibited consistently upregulated GLI1/SOX2OT/METTL3/14/IGF2BP2. The m6A-modified GLI1-SOX2OT loop may serve as a potential therapeutic target and prognostic predictor for lung cancer therapy and diagnosis in the clinic.

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“…Increasing evidence suggests that susceptibility to malignant CM is associated with SNPs [ 4 ]. GLI-1 polymorphisms in the hedgehog pathway are risk factors for melanoma susceptibility and can be used as prognostic biomarkers [ 5 ]. Furthermore, the IRF4 SNP (rs12203592) and the MTAP (rs869330) variants are both associated with melanoma-specific survival [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Single Nucleotide Polymorphism‐Related Genes in Tumour Immune Cell Infiltration and Prognosis of Cutaneous Melanoma

Wang

Liu

et al. 2023

BioMed Research International

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Background. Advances in cancer research have allowed for early diagnosis and improved treatment of cutaneous melanoma (CM). However, its invasiveness and recurrent metastasis, along with rising resistance to newer therapies, have lent urgency to the search for novel biomarkers and the underlying molecular mechanisms of CM. Methods. Single nucleotide polymorphism- (SNP-) related genes were obtained from the sequencing data of 428 CM samples in The Cancer Genome Atlas. Functional enrichment of these genes was analysed in clusterProfiler. Additionally, a protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Gene (STRING) database. Gene Expression Profiling Interactive Analysis (GEPIA) was used to identify the expression and prognostic value of mutated genes. Finally, the Tumour Immune Estimation Resource (TIMER) analysed the relationship between gene expression and immune cell infiltration. Results. We constructed a PPI network from the top 60 SNP-related genes. Mutated genes were mainly involved in calcium and oxytocin signalling pathways, as well as circadian entrainment. In addition, three SNP-related genes, BRAF, FLG, and SORL1, were significantly associated with patient prognosis. BRAF and SORL1 were positively associated with infiltration abundance of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells, whereas FLG expression was negatively associated. Furthermore, higher immune cell infiltration was positively correlated with good prognosis. Conclusions. Our study provides vital bioinformatic data and a relevant theoretical basis to further explore the molecular pathogenesis of CM and improve patient prognosis.

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GLI-1 polymorphisms of Hedgehog pathway as novel risk and prognostic biomarkers in melanoma patients

Cited by 7 publications

References 33 publications

PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

N6-methyladenine-mediated aberrant activation of the lncRNA SOX2OT-GLI1 loop promotes non-small-cell lung cancer stemness

Role of Single Nucleotide Polymorphism‐Related Genes in Tumour Immune Cell Infiltration and Prognosis of Cutaneous Melanoma

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