Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer

Balla, Bernadett; Tobiás, Bálint; Kósa, János P.; Podani, János; Horváth, Péter; Nagy, Zsolt; Horanyi, J; Járay, Balázs; Székely, Eszter; Krenács, László; Árvai, Kristóf; Dank, Magdolna; Putz, Zsuzsanna; Szabo, Barbara; Szili, Balázs; Valkusz, Zsuzsanna; Vasas, Béla; Gyõri, Gabriella; Lakatos, Péter L.; Takács, István

doi:10.1007/s40618-014-0165-7

Cited by 19 publications

(23 citation statements)

References 25 publications

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“…The association between enhanced CYP24A1 activity and tumorigenesis has been previously reported ( 8 ). Following transfection with CYP24A1 siRNA, CYP24A1 expression was significantly downregulated ( Fig.…”

Section: Resultssupporting

confidence: 57%

“…The primary effect of 1,25-D3 is to regulate bone and calcium homeostasis. However, this active form of vitamin D3 also exhibits non-classical effects, including regulation of the cell cycle and various anti-tumor effects, and is therefore attracting increased attention ( 6 – 8 ). It has been demonstrated that 1,25-D3 is implicated in various types of cancer ( 9 – 11 ), including thyroid cancer, where its concentration was reduced ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

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CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid cancer cells

Zhang

2018

Exp Ther Med

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It has been demonstrated that 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1) is a key enzyme that neutralizes vitamin D activity, which may have an anti-tumor effect. Therefore, the aim of the current study was to explore the effect of the active metabolite of vitamin D, 1,25-dihydroxyvitamin D (1,25-D3) on thyroid cancer cells following the downregulation of CYP24A1. A Cell Counting Kit-8 assay identified that CYP24A1 knockdown enhanced the anti-proliferative effects of 1,25-D3 on thyroid cancer cells. Furthermore, the results of the scratch wound and Transwell assays indicated that CYP24A1 knockdown enhanced the inhibitory effect of 1,25-D3 on cell migration. The results from reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that treatment with 1,25-D3 and CYP24A1 knockdown synergistically enhanced the expression of the epithelial-related gene E-cadherin and decreased the expression of the mesenchymal-related genes N-cadherin and vimentin. Following CYP24A1 knockdown and treatment with 1,25-D3, the expression of matrix metalloproteinase 2 and metalloproteinase inhibitor 1 were significantly decreased and increased, respectively, compared with the group that underwent treatment with 25-D3 alone. Furthermore, protein kinase B (Akt) and β-catenin activity was significantly decreased by this synergetic effect compared with the group that underwent treatment with 1,25-D3 alone. The results of the current study suggest that CYP24A1 knockdown contributes to the anti-tumor effect of 1,25-D3 and that this effect may be due to deactivation of the Akt and β-catenin signaling pathways. Therefore, CYP24A1 knockdown and 1,25-D3 treatment may be used synergistically as a novel therapeutic strategy to treat patients with thyroid cancer.

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Section: Resultssupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid cancer cells

Zhang

2018

Exp Ther Med

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“…PCR in tissue specimens of 60 patients (Zou et al 2014). The same was corroborated by Balla and co-workers who examined CYP24A1 expression by real-time quantitative PCR in normal and cancer tissue sections of 100 patients with PTC: tumor malignity variables (i. e., vascular invasion, lymph node involvement, tumor size, and hypothyreosis) correlated with CYP24A1 expression(Balla et al 2014). Resistance to calcitriol (and another VDR agonist) was observed in cells with high baseline…”

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confidence: 52%

Vitamin D in Thyroid Disorders

Kmieć

Sworczak

2015

Exp Clin Endocrinol Diabetes

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Vitamin D?s canonical role are its effects exerted on the musculoskeletal system. In the last decades the importance of this hormone has been studied in the context of extraskeletal health. Hypovitaminosis D and several polymorphic variants of genes coding proteins crucial in the transport, metabolism and effects of vitamin D have been associated with negative health outcomes. In this review the current state of knowledge on the role of vitamin D in thyroid disorders is presented. The review is based on a literature search of the PubMed database performed in December 2014. The following search terms were used in conjunction with ?vitamin D?: thyroid cancer, Graves?, Hashimoto, thyroiditis, autoimmune thyroid, AITD, nodules, hyperthyroidism, and hypothyroidism. Currently, similarly to other extraskeletal health outcomes, a clear role of vitamin D has not been demonstrated in thyroid disorders. Further research is necessary to fully elucidate the importance of vitamin D in case of thyroid disease.

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“…19 Similarly, others have shown that CYP24A1 is preferentially expressed to a greater degree in thyroid cancers with other somatic oncogenic mutations. 21 These data Figure 5. Complex relationship between cytochrome P450 family 24 subfamily A member 1 (CYP24A1) and KRAS.…”

Section: Discussionmentioning

confidence: 91%

Oncogenic Potential of CYP24A1 in Lung Adenocarcinoma

Shiratsuchi

Wang

Chen

et al. 2017

Journal of Thoracic Oncology

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Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer

Abstract: A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.

Cited by 19 publications

References 25 publications

CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid cancer cells

CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid cancer cells

Vitamin D in Thyroid Disorders

Oncogenic Potential of CYP24A1 in Lung Adenocarcinoma

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