Stem cell factor-mediated upregulation of SIRT1 protects melanin-deprived keratinocytes against UV-induced DNA damage in individuals with vitiligo.

Despite the loss of melanocytes, individuals with vitiligo have a significantly lower risk of developing skin malignancies compared to ethnicity-matched controls. The study investigated the molecular mechanisms that protect skin cells (keratinocytes) from UV-B-induced DNA damage in individuals with vitiligo. The study found that upregulation of stem cell factor (SCF) signaling significantly reduced γ-H2AX positivity and cyclobutane pyrimidine dimer formation and improved mitochondrial health (elongated mitochondria, reduced reactive oxygen species [ROS] and lipid peroxidation) in keratinocytes upon UV-B exposure.

Differential regulation of miR-21-5p delays wound healing of melanocyte-deprived vitiligo skin by modulating the expression of tumor-suppressors PDCD4 and Maspin.

The loss of melanocytes in vitiligo is associated with architectural, transcriptional, and cellular perturbations of keratinocytes and manifests as a reduced proliferation potential in vitro and delayed re-epithelialization in vivo. To understand the molecular mechanisms underlying this delay, microRNA (miRNA) profiling was performed on split skin biopsies collected on Day 1 (basal level) and Day 14 (wound re-epithelialization) from nonlesional (NL) and lesional (L) skin of five subjects with stable nonsegmental vitiligo and 129 miRNAs were found to be differentially regulated between the NL and L healed epidermis. miR-21-5p, expressed at comparable levels on NL and L Day 1 samples, demonstrated significant upregulation during re-epithelialization.

Integrated analysis of miRNA-mRNA networks reveals a strong anti-skin cancer signature in vitiligo epidermis.

Expression of microRNAs (miRNAs) is often dysregulated in several cancers, including non-melanoma skin cancer (NMSC). Individuals with vitiligo possess a deregulated miRnome along with a lower risk of developing NMSCs. We used data sets from our previously published studies on vitiligo epidermis to construct functional miRNA-mRNA networks to understand the molecular basis underlying the lower incidence of NMSC observed in individuals with vitiligo.

Probing the effects of double mutations on the versatile protein ubiquitin in Saccharomyces cerevisiae.

Ubiquitin is an indispensable protein of eukaryotic origin with an extraordinarily high degree of sequence conservation. It is used to tag proteins post-translationally and the process of ubiquitination regulates the activity of the modified proteins or drives them for degradation. Double mutations produce varied effects in proteins, depending on the structural relationship of the mutated residues, their role in the overall structure and functions of a protein.