Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types...

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Published in:Medical molecular morphology 2024-09, Vol.57 (3), p.185-199
Main Authors: Nakamori, Yuna, Takasawa, Akira, Takasawa, Kumi, Kyuno, Daisuke, Ono, Yusuke, Magara, Kazufumi, Nakahashi, Naoya, Sekiguchi, Shohei, Tsuchihashi, Kei, Miyazaki, Akihiro, Osanai, Makoto
Format: Article
Language:English
Subjects:
5-Fluorouracil
Anatomy
Antineoplastic drugs
Cancer
Cell death
Cell differentiation
Cell fate
Cell growth
Cell proliferation
Cisplatin
Enzymes
Homeostasis
Malignancy
Medical prognosis
Medicine
Medicine & Public Health
Molecular Medicine
Myc protein
Nucleotide sequence
Oral carcinoma
Oral squamous cell carcinoma
Original Paper
Pathology
Sequence analysis
Squamous cell carcinoma
Vitamin D
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Summary:Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.
ISSN:1860-1480
1860-1499
1860-1499
DOI:10.1007/s00795-024-00387-y