MicroRNA-203 regulates melanosome transport and tyrosinase expression in melanoma cells by targeting kinesin superfamily protein 5b
Open accessAbstract
MicroRNA (miR)-203 is known to be downregulated and to act as an anti-oncomir in melanoma cells. At present, we found that exogenous miR-203 increased pigmentation and protein expression levels of the melanoma antigen recognized by T cells (Melan-As/MART1s) and/or tyrosinase (TYR) in the human melanoma cells tested. Inversely, treatment with an inhibitor of miR-203 downregulated the expression level of TYR. The target gene of miR-203 involved in the mechanism was kinesin superfamily protein 5b (kif5b), which was revealed by gene silencing using short interfering RNA and luciferase activity assay. Furthermore, immunocytochemistry showed obvious accumulation of melanosomes around nuclei of human melanoma Mewo cells transfected with miR-203 or siR-kif5b. Importantly, treatment with the miR-203 inhibitor, but not miR-203, exhibited effects on human epidermal melanocytes isolated from lightly pigmented adult skin similar to those on melanoma cells. In addition, the data indicated that exogenous miR-203 also negatively regulated the cAMP response element-binding protein 1 (CREB1)/microphthalmia-associated transcription factor (MITF)/Rab27a pathway, which is one of the main pathways active in melanoma cells. In conclusion, our data indicated that anti-oncogenic miR-203 had a pivotal role in melanoma through reducing melanosome transport and promoting melanogenesis by targeting kif5b and through negative regulation of the CREB1/MITF/Rab27a pathway.
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Melanosome transport to the periphery of melanocytes precedes their transfer to neighboring keratinocytes.
“Melanosome transport to the periphery of melanocytes precedes their transfer to neighboring keratinocytes [ 32 , 33 , 34 ].”
From Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing (2023) · cites this paper as [33]
The Introduction (page unavailable) says melanosomes are transported from near the nucleus to the plasma membrane, supporting movement to the melanocyte periphery. Our copy does not describe their subsequent transfer to neighboring keratinocytes, so it does not establish the full sequence claimed. (LLM, conf=0.85)
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- Authors
- Noguchi, S., Kumazaki, M., Yasui, Y., Mori, T., Yamada, N., & Akao, Y.
- Affiliations
- Gifu University (JP)
- Corresponding author
- Noguchi, Shunsuke
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 134
- Issue
- 2
- Pages
- 461-469
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W1984811431
- Cited by
- 82
- References
- 34
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 13 · 2014: 9
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- miR-203, KIF5B, melanosome transport, tyrosinase, melanoma, melanogenesis, epidermal melanocytes, CREB1, MITF, Rab27a, microRNA target regulation
- MeSH terms
- Epidermal Cells, Biological Transport, Humans, Melanocytes, Melanoma, Skin Neoplasms, Monophenol Monooxygenase, Signal Transduction, Kinesins, Myosin Heavy Chains, Melanosomes, Myosin Type V, RNA, Small Interfering, MicroRNAs, Cell Line, Tumor, Cell Proliferation
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