ArticleBMC cancer2018
Coordinated expression and genetic polymorphisms in Grainyhead-like genes in human non-melanoma skin cancers.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Vitamin D Receptor Regulates the Expression of the Grainyhead-Like 1 Gene.International journal of molecular sciences · 2024Article
- Dual role of GRHL3 in bladder carcinogenesis depending on histological subtypes.Molecular oncology · 2024Article
- Dysregulation of Grainyhead-like 3 expression causes widespread developmental defects.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma.International journal of molecular sciences · 2023Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
- GRHL3 Promotes Tumor Growth and Metastasis via the MEK Pathway in Colorectal Cancer.Analytical cellular pathology (Amsterdam) · 2021Article
- Transcription factors Krüppel-like factor 4 and paired box 5 regulate the expression of the Grainyhead-like genes.PloS one · 2021Article
- Grainyhead-like transcription factors in cancer - Focus on recent developments.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Relationship between Single Nucleotide Polymorphisms ofInternational journal of molecular and cellular medicine · 2020Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe Grainyhead-like (GRHL) transcription factors have been linked to many different types of cancer. However, no previous study has attempted to investigate potential correlations in expression of different GRHL genes in this context. Furthermore, there is very little information concerning damaging mutations and/or single nucleotide polymorphisms in GRHL genes that may be linked to cancer.
methodsDNA and RNA were extracted from human non-melanoma skin cancers (NMSC) and adjacent normal tissues (n = 33 pairs of samples). The expression of GRHL genes was measured by quantitative real time PCR. Regulation of GRHL expression by miRNA was studied using cell transfection methods and dual-luciferase reporter system. Targeted deep sequencing of GRHL genes in tumor samples and control tissues were employed to search for mutations and single nucleotide polymorphisms. Single marker rs141193530 was genotyped with pyrosequencing in additional NMSC replication cohort (n = 176). Appropriate statistical and bioinformatic methods were used to analyze and interpret results.
resultsWe discovered that the expression of two genes - GRHL1 and GRHL3 - is reduced in a coordinated manner in tumor samples, in comparison to the control healthy skin samples obtained from the same individuals. It is possible that both GRHL1 and GRHL3 are regulated, at least to some extent, by different strands of the same oncogenic microRNA - miR-21, what would at least partially explain observed correlation. No de novo mutations in the GRHL genes were detected in the examined tumor samples. However, some single nucleotide polymorphisms in the GRHL genes occur at significantly altered frequencies in the examined group of NMSC patients.
conclusionsNon-melanoma skin cancer growth is accompanied by coordinated reduced expression of epidermal differentiation genes: GRHL1 and GRHL3, which may be regulated by miR-21-3p and -5p, respectively. Some potentially damaging single nucleotide polymorphisms in GRHL genes occur with altered frequencies in NMSC patients, and they may in particular impair the expression of GRHL3 gene or functioning of encoded protein. The presence of these polymorphisms may indicate an increased risk of NMSC development in affected people.
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