Importance of microRNAs in Skin Oncogenesis and Their Suitability as Agents and Targets for Topical Therapy

Gerloff, Dennis; Sunderkötter, Cord; Wohlrab, Johannes

doi:10.1159/000509879

Cited by 16 publications

(6 citation statements)

References 131 publications

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“…MicroRNAs are involved in development or progression of cancer, but obviously also in mechanisms of drug resistance in leukaemia and in various solid cancers [ 26 , 27 , 28 , 29 , 30 ]. They could present potential therapeutic targets, by the use of chemically modified complementary RNA molecules, such as locked nucleic acids (LNAs) or miRNA mimics [ 31 , 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma

Gebhardt

Edemir

Groß

et al. 2021

Cancers

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Many melanomas are associated with activating BRAF mutation. Targeted therapies by inhibitors of BRAF and MEK (BRAFi, MEKi) show marked antitumor response, but become limited by drug resistance. The mechanisms for this are not fully revealed, but include miRNA. Wishing to improve efficacy of BRAFi and knowing that certain miRNAs are linked to resistance to BRAFi, we wanted to focus on miRNAs exclusively associated with response to BRAFi. We found increased expression of miR-129-5p during BRAFi treatment of BRAF- mutant melanoma cells. Parallel to emergence of resistance we observed mir-129-5p expression to become suppressed by BRAF/EZH2 signaling. In functional analyses we revealed that miR-129-5p acts as a tumor suppressor as its overexpression decreased cell proliferation, improved treatment response and reduced viability of BRAFi resistant melanoma cells. By protein expression analyses and luciferase reporter assays we confirmed SOX4 as a direct target of mir-129-5p. Thus, modulation of the miR-129-5p-SOX4 axis could serve as a promising novel strategy to improve response to BRAFi in melanoma.

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Section: Introductionmentioning

confidence: 99%

BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma

Gebhardt

Edemir

Groß

et al. 2021

Cancers

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“…MiRNAs can act as tumor suppressors or promoters. However, they are very prone to degradation by exonucleases 138 . Exogenous factors like UV radiation can modulate miRNAs and their targets.…”

Section: Discussionmentioning

confidence: 99%

Molecular and immune targets in cutaneous squamous cell carcinoma

Galambus

Tsai

2022

Molecular Carcinogenesis

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Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and often confers a good prognosis. Though surgery is the gold standard of treatment, unresectable or metastatic disease can necessitate systemic therapy. Of systemic agents, there is increasing interest in the use of immunotherapies and targeted therapy. Further study into the driver mutations in cSCC has identified opportunities for targeted therapy. In this review, we discuss both current and investigational immune and molecular targets of therapy for cSCC.

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“…Further investigations using advanced in vitro models, such as co-culture of skin cells and organotypic skin culture, are to be encouraged in order to better clarify the essential role of miRNAs in melanogenesis, taking into account the strict correlation among cells that participate in the process [ 99 ]. Epigenetic regulation of melanogenesis provides a novel insight into the melanogenesis mechanism and suggests potential therapeutic approaches for the unsolved problem of skin pigmentation disorders [ 7 ], based on the use of miRNA mimics and antagomiRs [ 52 , 100 ].…”

Section: Discussionmentioning

confidence: 99%

microRNAs in the Regulation of Melanogenesis

Hushcha¹,

Blo

Otòn-Gonzalez

et al. 2021

IJMS

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Melanogenesis is the process leading to the synthesis of melanin, the main substance that influences skin color and plays a pivotal role against UV damage. Altered melanogenesis is observed in several pigmentation disorders. Melanogenesis occurs in specialized cells called melanocytes, physically and functionally related by means of autocrine and paracrine interplay to other skin cell types. Several external and internal factors control melanin biosynthesis and operate through different intracellular signaling pathways, which finally leads to the regulation of microphthalmia-associated transcription factor (MITF), the key transcription factor involved in melanogenesis and the expression of the main melanogenic enzymes, including TYR, TYRP-1, and TYRP-2. Epigenetic factors, including microRNAs (miRNAs), are involved in melanogenesis regulation. miRNAs are small, single-stranded, non-coding RNAs, of approximately 22 nucleotides in length, which control cell behavior by regulating gene expression, mainly by binding the 3′ untranslated region (3′-UTR) of target mRNAs. This review collects data on the miRNAs involved in melanogenesis and how these miRNAs can modulate target gene expression. Bringing to light the biological function of miRNAs could lead to a wider understanding of epigenetic melanogenesis regulation and its dysregulation. This knowledge may constitute the basis for developing innovative treatment approaches for pigmentation dysregulation.

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Importance of microRNAs in Skin Oncogenesis and Their Suitability as Agents and Targets for Topical Therapy

Cited by 16 publications

References 131 publications

BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma

BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma

Molecular and immune targets in cutaneous squamous cell carcinoma

microRNAs in the Regulation of Melanogenesis

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