Loss of miR-101-3p in melanoma stabilizes genomic integrity, leading to cell death prevention

Lämmerhirt L, Kappelmann-Fenzl M, Fischer S, Meier P, Stäbler S, Kuphal S, Boßerhoff AK (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Cellular & Molecular Biology Letters Springer Verlag (Germany)

Book Volume: 29

Article Number: 29

Journal Issue: 1

DOI: 10.1186/s11658-024-00552-2

Abstract

Malignant melanoma remains the most lethal form of skin cancer, exhibiting poor prognosis after forming distant metastasis. Owing to their potential tumor-suppressive properties by regulating oncogenes and tumor suppressor genes, microRNAs are important player in melanoma development and progression. We defined the loss of miR-101-3p expression in melanoma cells compared with melanocytes and melanoblast-related cells as an early event in tumor development and aimed to understand the tumor suppressive role of miR-101-3p and its regulation of important cellular processes. Reexpression of miR-101-3p resulted in inhibition of proliferation, increase in DNA damage, and induction of apoptosis. We further determined the nuclear structure protein Lamin B1, which influences nuclear processes and heterochromatin structure, ATRX, CASP3, and PARP as an important direct target of miR-101-3p. RNA sequencing and differential gene expression analysis after miR-101-3p reexpression supported our findings and the importance of loss of mir-101-3p for melanoma progression. The validated functional effects are related to genomic instability, as recent studies suggest miRNAs plays a key role in mediating this cellular process. Therefore, we concluded that miR-101-3p reexpression increases the genomic instability, leading to irreversible DNA damage, which leads to apoptosis induction. Our findings suggest that the loss of miR-101-3p in melanoma serves as an early event in melanoma progression by influencing the genomic integrity to maintain the increased bioenergetic demand.

Authors with CRIS profile

Lisa Lämmerhirt Lehrstuhl für Biochemie und Molekulare Medizin Sebastian Stäbler Lehrstuhl für Biochemie und Molekulare Medizin Silke Kuphal Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

Technische Hochschule Deggendorf DE Germany (DE)

How to cite

APA:

Lämmerhirt, L., Kappelmann-Fenzl, M., Fischer, S., Meier, P., Stäbler, S., Kuphal, S., & Boßerhoff, A.K. (2024). Loss of miR-101-3p in melanoma stabilizes genomic integrity, leading to cell death prevention. Cellular & Molecular Biology Letters, 29(1). https://doi.org/10.1186/s11658-024-00552-2

MLA:

Lämmerhirt, Lisa, et al. "Loss of miR-101-3p in melanoma stabilizes genomic integrity, leading to cell death prevention." Cellular & Molecular Biology Letters 29.1 (2024).

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