miR-34 modulates apoptotic gene expression in Ingenol mebutate treated keloid fibroblasts

Abstract

Keloids are benign skin tumors that develop in individuals who have a positive family history of keloid disorders. Keloids are characterized by a deregulated wound-healing process, atypical fibroblasts with extreme deposition of extracellular matrix components, particularly collagen, increased cell proliferation and associated failure of apoptosis. Recently ingenol-mebutate has been used as a novel agent with anti-proliferative activity on human keloids as an alternative treatment option in patients, once conventional therapies have failed. We hypothesized that microRNAs (miR/miRNA) may be involved in the balance between lesion formation and repair. A comprehensive understanding of the molecular mechanism underlying the Ingenol-mebutate response in keloid fibroblast following Ingenol-mebutate exposure has been established previously. Therefore, the present study analyzed changes in miRNAs and apoptotic gene regulation in Ingenol-mebutate treated keloid fibroblast, by reverse transcription-quantitative polymerase chain reaction and a DNA fragmentation assay. The range of upregulated miRNAs and downregulated genes encoding cell death appeared to be associated with the degree of the morphological alterations in Ingenol-mebutate treated keloids. In particular, the upregulation of miR-34a was detected in keloid fibroblasts during and following Ingenol-mebutate exposure. Keloid fibroblasts that overexpressed miR-34a showed differential expression of genes involved in the apoptotic signaling pathway such as p53. In conclusion, the Ingenol-mebutate treatment used here was effective in reducing keloid fibroblast growth in cell culture experiments and the expression of particular miRNAs modulated the pro-apoptotic gene expression following Ingenol-mebutate treatment.

Retracted: Baicalein retards proliferation and collagen deposition by activating p38MAPK‐JNK via microRNA‐29

“…17 The innovative and targeted therapeutics have recently drawn our attention by medicating the expression of miRs for curing these diseases. [18][19][20] In the current study, we found Fibroblast NIH-3T3 cells were pretreated with BAI (150 μM) for 12 hours after transfection of miR-29 inhibitor and its consistent NC. Fibroblast NIH-3T3 cells did not accept the transfection of miR-29 inhibitor or pretreatment of BAI in the CTRL.…”

“…These exuberant responses start the formation of collagen and even keloids . The innovative and targeted therapeutics have recently drawn our attention by medicating the expression of miRs for curing these diseases . In the current study, we found that BAI effectively eliminated the proliferation of fibroblast cells and TGF‐β1‐induced synthesis of collagen.…”

Identification of differentially expressed circular RNAs in keloid and normal skin tissue by high‐throughput sequencing

“…Therefore, there are reasons to think that noncoding RNAs may be involved in the pathogenesis of keloid. 10,11 Circular RNAs (circRNAs), a family of endogenous noncoding RNA, characterized by unique structure, broad expression, spatiotemporal specificity, and evolutionary conservation, which suggests that these molecules are unlikely nonfunctional byproducts, but are essential transcripts having potential roles both physiologically and pathologically. In addition, unique attributes of circRNAs, such as high stableness, protection from exonucleolytic decay, and presence at body fluids, suggest a promising application prospect for circRNAs in molecular biomarkers for diagnosis, noninvasive monitoring, prognosis, and therapeutic targets for many diseases.…”

“…Compared with normal tissues and fibroblasts, keloid and keloid fibroblasts express different levels of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Therefore, there are reasons to think that noncoding RNAs may be involved in the pathogenesis of keloid 10,11 …”

Impact of human adipose tissue-derived stem cells on dermatofibrosarcoma protuberans cells in an indirect co-culture: an in vitro study

“…Interestingly, according to studies, in keloid, one of the benign skin tumors [ 63 ], ADSCs could reduce the expression of COL1A1 in keloid fibroblasts and deposition of collagen in keloid tissue ex vivo. Currently, the reasons and mechanisms for these differential impacts of ADSCs on benign and malignant tumors are unclear.…”