Evaluation of circulating serum 3 types of microRNA as biomarkers of oral squamous cell carcinoma; A pilot study

Introduction: The microRNAs are molecules which have important biologic role and play key point in cancers. The aim of present study was to determine the miR-21, miR-24, and miR-29a expression in serum of patients with oral squamous cell carcinoma. Materials and methods: Blood samples were obtained from 40 patients (20 in cases and 20 in control group) to determine the miR-21, miR-24, and miR-29a expressions by using real-time PCR and �CT. Results: Mean miR-29a was �2.28 ± 2.15 and 5.61 ± 2.38 in case and control groups, respectively. The miR-21 was 6.90 ± 3.86 and �0.88 ± 2.31 in case and control groups, respectively. According to the results, miR-24 was 2.13 ± 2.89 and �0.35 ± 2.44 in case and control, respectively. A significant difference was observed on miR-21, miR-24, and miR-29a between two groups (P <.05). The results obtained by t test showed miR-21 and miR-24 were higher and miR-29a was lower in plasma of oral squamous cell carcinoma patients and this differences were significant (P <.05). Conclusion: These results suggested miR-21, miR-24, and miR-29a in serum of patients with oral squamous cell carcinoma comparing with normal group can be used as potent markers for carcinoma detection and also may be a potentially therapeutic approach in the future. More longitudinal studies with larger samples are necessary to confirm these findings. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Lt

A novel DLX3–PKC integrated signaling network drives keratinocyte differentiation

Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKCα by transgenic targeting (K5-PKCα), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKCα activation, suggesting a feedback regulation of DLX3 and PKCα. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3–PKCα signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis