miR-129-5p inhibits anchorage-independent growth through silencing of ACTN1 and the ELK4/c-FOS axis in HPV-transformed keratinocytes.

A persistent infection with human papillomavirus (HPV) can induce precancerous lesions of the cervix that may ultimately develop into cancer. Cervical cancer development has been linked to altered microRNA (miRNA) expression, with miRNAs regulating anchorage-independent growth being particularly important for the progression of precancerous lesions to cancer. In this study, we set out to identify and validate targets of miR-129-5p, a previously identified tumor suppressive miRNA involved in anchorage-independent growth and HPV-induced carcinogenesis. We predicted 26 potential miR-129-5p targets using online databases, followed by KEGG pathway enrichment analysis. RT-qPCR and luciferase assays confirmed that 3'UTR regions of six genes (ACTN1, BMPR2, CAMK4, ELK4, EP300, and GNAQ) were targeted by miR-129-5p. Expressions of ACTN1, CAMK4, and ELK4 were inversely correlated to miR-129-5p expression in HPV-transformed keratinocytes, and their silencing reduced anchorage-independent growth. Concordantly, miR-129-5p overexpression decreased protein levels of ACTN1, BMPR2, CAMK4 and ELK4 in anchorage-independent conditions. Additionally, c-FOS, a downstream target of ELK4, was downregulated upon miR-129-5p overexpression, suggesting regulation through the ELK4/c-FOS axis. ACTN1 and ELK4 expression was also upregulated in high-grade precancerous lesions and cervical cancers, supporting their clinical relevance. In conclusion, we identified six targets of miR-129-5p involved in the regulation of anchorage-independent growth, with ACTN1, BMPR2, ELK4, EP300, and GNAQ representing novel targets for miR-129-5p. For both ACTN1 and ELK4 functional and clinical relevance was confirmed, indicating that miR-129-5p-regulated ACTN1 and ELK4 expression contributes to HPV-induced carcinogenesis.

Expanding the Psoriasis Framework: Immunopathogenesis and Treatment Updates.

Psoriasis is a chronic heterogeneous condition with multiple available treatment options that have resulted in dramatic disease improvements for patients. IL-23/IL-17 signaling is the central immune signaling pathway driving psoriasis, though recent research has uncovered other key contributing signals such as IL-17C, IL-17F, IL-36, and tyrosine kinase 2 (TYK2). Novel therapeutic targets inhibiting these cytokines have expanded our understanding of the pathogenesis of psoriasis. IL-23/IL-17 signaling is critical for the development of epidermal hyperplasia and the mature psoriatic plaque in susceptible individuals. Increased IL-17 and IL-23 expression works synergistically with other cytokines, such as IL-12, IL-22, IL-36, tumor necrosis factor (TNF), and interferon (IFN), to help create a self-sustaining, feed-forward circuit in keratinocytes, which contributes to the chronicity of the disease. This clinical review highlights recent discoveries in the immunopathogenesis of psoriasis and summarizes new antipsoriasis therapies targeting IL-36, IL-17F, aryl hydrocarbon receptors (AHRs), phosphodiesterase 4 (PDE4), and TYK2 signaling. Despite recent success in the treatment of psoriasis, continued research is needed to further advance disease understanding and shape management strategies.

Gasdermin E promotes translocation of p65 and c-jun into nucleus in keratinocytes for progression of psoriatic skin inflammation.

Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme-/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1ß, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.

Excision pathways for keratinocyte cancers diagnosed by teledermatology: a retrospective review.

Introduction The New Zealand population has one of the highest incidences of skin cancer in the world. Hospital waiting lists for surgical excision of keratinocytic skin cancers (basal cell carcinoma and squamous cell carcinoma) are lengthy, and increasingly, excisions are undertaken in primary care. Teledermatology, in response to general practitioners' electronic referrals (e-referrals), can improve clinical communication between general practitioners and dermatologists. Aim The aim of this study was to evaluate an excision pathway for keratinocytic cancers diagnosed by teledermatology. Methods A retrospective observational descriptive review of a 3-month cohort of primary care e-referrals was undertaken. Results Three hundred and fifty eight suspected keratinocytic cancers (KCs) were diagnosed by teledermatology; histology reports confirmed KC in 201 of 267 excisions (75%). The majority (77.2%) were excised by general practitioners an average of 25 days after the dermatologist's recommendation. The rest were excised by plastic surgeons in private (3.4%) or at a public hospital (19.5%) after an average of 40 or 134 days, respectively. Discussion E-referral pathways are now widely implemented. However, the ideal workflow for skin cancer management is unknown. We have demonstrated in New Zealand that surgery can be undertaken in primary care within a month of a teledermatology diagnosis and excision recommendation. Conclusion This study reports prompt excision of KCs by general practitioners after an e-referral and a teledermatology response.

Effects of COVID-19 Pandemic on the Diagnosis of Melanoma and Keratinocyte Carcinomas: a Systematic Review and Meta-analysis.

Since December 2019, the COVID-19 pandemic has profoundly affected healthcare. The real effects of the COVID-19 pandemic on skin cancer are still unclear, more than 3 years later. This study aims to summarise the pandemic's impact on skin cancer diagnosis and outcome. A systematic review and meta-analysis was conducted, selecting studies comparing skin cancer diagnosis and prognosis post-pandemic with pre-pandemic data. A total of 27 papers were reviewed including 102,263 melanomas and 271,483 keratinocyte carcinomas. During the initial pandemic months (January-July 2020), melanoma surgeries dropped by 29.7% and keratinocyte carcinomas surgeries by 50.8%. Early pandemic tumours exhibited greater thickness and stage. In a long-term period beyond the initial months, melanoma surgeries decreased by 9.3%, keratinocyte carcinomas by 16.6%. No significant differences were observed in the Breslow thickness of melanomas after the start of the pandemic (mean difference 0.06, 95% confidence interval -0.46, 0.58). Melanomas operated on post-pandemic onset had an increased risk of ulceration (odds ratio 1.35, 95% confidence interval 1.22-1.50). Keratinocyte carcinomas showed increased thickness and worsened stage post-pandemic. However, studies included were mostly retrospective and cross-sectional, reporting diverse data. This review indicates that the pandemic likely caused delays in skin cancer diagnosis and treatment, potentially impacting patient outcomes.

The human papillomavirus late life cycle and links to keratinocyte differentiation.

Regulation of human papillomavirus (HPV) gene expression is tightly linked to differentiation of the keratinocytes the virus infects. HPV late gene expression is confined to the cells in the upper layers of the epithelium where the virus capsid proteins are synthesized. As these proteins are highly immunogenic, and the upper epithelium is an immune-privileged site, this spatial restriction aids immune evasion. Many decades of work have contributed to the current understanding of how this restriction occurs at a molecular level. This review will examine what is known about late gene expression in HPV-infected lesions and will dissect the intricacies of late gene regulation. Future directions for novel antiviral approaches will be highlighted.

Interleukins and Psoriasis.

Psoriasis is an immune-mediated chronic inflammatory skin disease that affects 2% to 3% of the world's population. It is widely assumed that immune cells and cytokines acting together play a crucial part in the pathophysiology of psoriasis by promoting the excessive proliferation of skin keratinocytes and inflammatory infiltration. Interleukins (ILs), as a critical component of cytokines, have been closely associated with the pathogenesis and progression of psoriasis. This review summarizes the current contribution of ILs to psoriasis and describes the role each IL performs in psoriasis. Furthermore, the paper presents the therapeutic effects and application prospects of biologics developed for ILs in clinical treatment and experiments. The study aims to further the research on ILs in the treatment of psoriasis.

PTPN2 inhibits the proliferation of psoriatic keratinocytes by dephosphorylation of STAT3.

Psoriasis is a recurrent and protracted disease that severely impacts the patient's physical and mental health. Thus, there is an urgent need to explore its pathogenesis to identify therapeutic targets. The expression level of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) was analyzed by immunohistochemistry techniques in psoriatic tissues and imiquimod-induced psoriatic mouse models. PTPN2 and signal transducer and activator of transcription 3 (STAT3) were overexpressed or silenced in human keratinocytes or an interleukin (IL)-6-induced psoriasis HaCaT cell model using overexpression plasmid transfection or small interfering RNA technology in vitro, and the effects of PTPN2 on STAT3, HaCaT cell function, and autophagy levels were investigated using reverse transcription-quantitative polymerase chain reaction, Western blot, Cell Counting Kit 8, 5-ethynyl-20-deoxyuridine, flow cytometry, and transmission electron microscopy. PTPN2 expression was found to be significantly downregulated in psoriatic tissues. Then, the in vitro antipsoriatic properties of PTPN2 were investigated in an IL-6-induced psoriasis-like cell model, and the results demonstrated that inhibition of keratinocyte proliferation by PTPN2 may be associated with elevated STAT3 dephosphorylation and autophagy levels. These findings provide novel insights into the mechanisms of autophagy in psoriatic keratinocytes and may be essential for developing new therapeutic strategies to improve inflammatory homeostasis in psoriatic patients.

IL-6 Up-Regulates Expression of LIM-Domain Only Protein 4 in Psoriatic Keratinocytes through Activation of the MEK/ERK/NF-κB Pathway.

Psoriasis is a chronic inflammatory skin disease characterized by the activation of keratinocytes and the infiltration of immune cells. Overexpression of the transcription factor LIM-domain only protein 4 (LMO4) promoted by IL-23 has critical roles in regulating the proliferation and differentiation of psoriatic keratinocytes. IL-6, an autocrine cytokine in psoriatic epidermis, is a key mediator of IL-23/T helper 17-driven cutaneous inflammation. However, little is known about how IL-6 regulates the up-regulation of LMO4 expression in psoriatic lesions. In this study, human immortalized keratinocyte cells, clinical biopsy specimens, and an animal model of psoriasis induced by imiquimod cream were used to investigate the role of IL-6 in the regulation of keratinocyte proliferation and differentiation. Psoriatic epidermis showed abnormal expression of IL-6 and LMO4. IL-6 up-regulated the expression of LMO4 and promoted keratinocyte proliferation and differentiation. Furthermore, in vitro and in vivo studies showed that IL-6 up-regulates LMO4 expression by activating the mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK)/NF-κB signaling pathway. These results suggest that IL-6 can activate the NF-κB signaling pathway, up-regulate the expression of LMO4, lead to abnormal proliferation and differentiation of keratinocytes, and promote the occurrence and development of psoriasis.

TRPM2-dependent autophagy inhibition exacerbates oxidative stress-induced CXCL16 secretion by keratinocytes in vitiligo.

Vitiligo is a depigmented skin disease due to the destruction of melanocytes. Under oxidative stress, keratinocyte-derived chemokine C-X-C motif ligand 16 (CXCL16) plays a critical role in recruiting CD8+ T cells, which kill melanocytes. Autophagy serves as a protective cell survival mechanism and impairment of autophagy has been linked to increased secretion of the proinflammatory cytokines. However, the role of autophagy in the secretion of CXCL16 under oxidative stress has not been investigated. Herein, we initially found that autophagy was suppressed in both keratinocytes of vitiligo lesions and keratinocytes exposed to oxidative stress in vitro. Autophagy inhibition also promoted CXCL16 secretion. Furthermore, upregulated transient receptor potential cation channel subfamily M member 2 (TRPM2) functioned as an upstream oxidative stress sensor to inhibit autophagy. Moreover, TRPM2-mediated Ca2+ influx activated calpain to shear autophagy related 5 (Atg5) and Atg12-Atg5 conjugate formation was blocked to inhibit autophagy under oxidative stress. More importantly, Atg5 downregulation enhanced the binding of interferon regulatory factor 3 (IRF3) to the CXCL16 promoter region by activating Tank-binding kinase 1 (TBK1), thus promoting CXCL16 secretion. These findings suggested that TRPM2-restrained autophagy promotes CXCL16 secretion via the Atg5-TBK1-IRF3 signaling pathway under oxidative stress. Inhibition of TRPM2 may serve as a potential target for the treatment of vitiligo. © 2024 The Pathological Society of Great Britain and Ireland.

Ex vivo confocal microscopy features of common benign lesions that mimic non-melanoma skin cancers: Towards clinical integration.

Ex vivo confocal microscope (EVCM) rapidly images freshly excised tissue at a histopathological resolution. EVCM features of keratinocyte skin cancers are well-established, but those of benign clinical mimickers remain scarce. We describe EVCM features of common benign lesions and compare them with their malignant differentials. EVCM was used to image 14 benign and 3 cancer tissues. We compared EVCM features of benign lesions with corresponding histopathology and with those of keratinocyte cancers. Key features of benign lesions were identified and differentiated from malignant lesions. Elastin and fat appeared prominent in EVCM; while koilocytes and melanin were difficult to identify. Visualization of entire epidermis was challenging due to difficulty of tissue flattening during imaging. Benign lesions can be differentiated from keratinocyte cancers with EVCM. Using EVCM, a rapid, bedside diagnosis and management of skin neoplasms is possible, especially in a remote location without a histopathology lab.

Application of bacteriophage φPaP11-13 attenuates rat Cutibacterium acnes infection lesions by promoting keratinocytes apoptosis via inhibiting PI3K/Akt pathway.

Acne vulgaris caused by antibiotic-resistant Cutibacterium acnes (C. acnes) infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the mechanism of phage treatment is inadequate. This research investigates the underlying molecular mechanisms of phage φPaP11-13 attenuating C. acnes-induced inflammation in rat models. We found that rats infected with C. acnes had higher average ear thickness, greater enrichment of inflammatory cells as shown by hematoxylin-eosin (HE) staining, and fewer TUNEL (TdT-mediated dUTP Nick-End Labeling)-positive keratinocytes visualized by IF staining. Moreover, an increase of IGF-1 and IGF-1 receptor (IGF-1r) was detected using the immunohistochemical (IHC) staining method, Western blot (WB), and quantitative real-time PCR (qRT-PCR) when infected with C. acnes, which was decreased after the application of phage φPaP11-13. By applying the IGF-1 antibody, it was demonstrated that the severity of C. acnes-induced inflammation was relevant to the expression of IGF-1. Through WB and qRT-PCR, activation of the PI3K/Akt pathway and a down-regulation of the BAD-mediated apoptosis pathway were discovered after C. acnes infection. Subsequently, it was shown that the activation of the PI3K/Akt pathway against BAD-mediated apoptosis pathway was alleviated after applying phage φPaP11-13. Furthermore, applying the IGF-1r inhibitor, Pan-PI3K inhibitor, and Akt inhibitor reversed the changing trends of BAD induced by C. acnes and phage φPaP11-13. This study demonstrates that one of the critical mechanisms underlying the attenuation of acne vulgaris by phage φPaP11-13 is lysing C. acnes and regulating keratinocyte apoptosis via the PI3K/Akt signaling pathway.IMPORTANCECutibacterium acnes infection-induced acne vulgaris may cause severe physical and psychological prognosis. However, the overuse of antibiotics develops drug resistance, bringing challenges in treating Cutibacterium acnes. Bacteriophages are currently proven effective in MDR (multiple drug-resistant) Cutibacterium acnes, but there is a significant lack of understanding of phage therapy. This study demonstrated a novel way of curing acne vulgaris by using phages through promoting cell death of excessive keratinocytes in acne lesions by lysing Cutibacterium acnes. However, the regulation of this cell cycle has not been proven to be directly mediated by phages. The hint of ternary relation among "phage-bacteria-host" inspires huge interest in future phage therapy studies.

Is the presence of Merkel cell polyomavirus and human papillomavirus DNA in keratinocyte cancers and precancers associated with HIV status? A case-control study.

The epidemiology and potential pathogenic roles of human papillomavirus (HPV) and Merkel cell polyomavirus (MCV) in keratinocyte cancers (KCs) arising in people living with HIV (PLWH) compared with HIV-negative individuals are poorly understood. These issues were investigated by a case-control study in which the presence of MCV and HPV DNA was identified by polymerase chain reaction in microdissected formalin-fixed paraffin-embedded tissue from PLWH and HIV-negative individuals. The samples comprised 190 cutaneous and genital KCs/precancers (actinic keratoses, n = 43; cutaneous squamous cell carcinoma (cSCC) in situ, n = 24; basal cell carcinoma, n = 78; cSCC, n = 34; penile carcinoma in situ, n = 9; penile SCC, n = 2 from 104 individuals (PLWH, n = 51; HIV-negative, n = 53). Almost one-quarter of samples were positive for MCV: this was not significantly associated with either HIV status (P = 0.06) nor lesion type. Overall, 36% (16/44) of MCV-positive lesions were coinfected with HPV; this was also not associated with HIV status. These findings indicate that if these viruses do contribute to the pathogenesis of KCs, it is likely to be independent of HIV status.

Survival of patients with basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma in situ: A whole population study.

BACKGROUND: Keratinocyte carcinoma (KC) is the commonest type of malignancy in humans; however, the impact of KC on survival is poorly understood. OBJECTIVES: This study characterizes the impact of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in situ (SCCis) on the survival of Icelanders. METHODS: This whole population study evaluated relative survival of KC in Iceland by using a cancer registry containing records of all BCC, SCCis, and SCC cases recorded in Iceland between 1981 and 2015. RESULTS: Between 1981 and 2015, 8767 Icelanders were diagnosed with their first localized KC. A total of 6473 individuals with BCC, 1194 with SCCis, and 1100 with invasive SCC, respectively. BCC was not associated with decreased survival except for men diagnosed with BCC between 1981 and 1995 for whom decreased 10-year relative survival was observed (85.3, 95% CI [77.9-92.7]). SCC and SCCis were both associated with a decrease in relative survival for certain population subgroups such as individuals <50 years of age at time of diagnosis. CONCLUSION: Our whole population cohort survival study examining the Icelandic Cancer Registry supports prior studies demonstrating that BCC is not associated with a reduction in relative survival and that SCC and SCCis are associated with comparatively poor relative survival in certain population subgroups.

METTL14 promotes IL-6-induced viability, glycolysis and inflammation in HaCaT cells via the m6A modification of TRIM27.

Interleukin-6 (IL-6) is a cytokine generated by healthy constituents of the skin, but is also up-regulated by a wide range of skin lesions and inflammatory conditions to trigger cytopathy of skin cells. TRIM27 was identified to contribute to the functional effects of IL-6 on skin cells. However, the underlying mechanism was not clear. Lentivirus infection was used for gene overexpression or silencing. RT-PCR and Western blot were used to respectively assess mRNA and protein levels. Cell viability was assessed by CCK-8 assay. Extracellular flux analysis was used to assess the levels of oxygen consumption rate and extracellular acidification rate. Mouse back skin was treated with imiquimod to produce psoriasis-like inflammation in vivo. Histological assessment and immunohistochemistry staining were respectively applied to analyse lesioned mouse and human skin samples. IL-6-induced increased viability, glycolysis and inflammation in keratinocytes was inhibited both by a chemical methylation inhibitor and by METTL14 knockdown. Further investigation found that METTL14 induces m6A methylation of TRIM27, which is recognized by a m6A reader, IGF2BP2. Elevation of TRIM27 level and activation of IL-6/STAT3 signalling pathway were found in an in vivo psoriasis-like inflammation model, whereas inhibition m6A methylation strongly alleviated the inflammation. Finally, METTL14, TRIM27, STAT3, p-STAT3 and IL-6 expressions were all found to be increased in clinical skin samples of psoriatic patients. Our results unravelled METTL14/TRIM27/IGF2BP2 signalling axis in keratinocyte cytopathy, which plays a critical role in facilitating the activation of IL-6/STAT3 signalling pathway. Our findings should provide inspirations for the design of new therapeutics for skin inflammatory diseases including psoriasis.

Pressure and Skin: A Review of Disease Entities Driven or Influenced by Mechanical Pressure.

Skin perceives and reacts to external mechanical forces to create resistance against the external environment. Excessive or inappropriate stimuli of pressure may lead to cellular alterations of the skin and the development of both benign and malignant skin disorders. We conducted a comprehensive literature review to delve into the pressure-induced and aggravated skin disorders and their underlying pressure-related mechanisms. Dysregulated mechanical responses of the skin give rise to local inflammation, ischemia, necrosis, proliferation, hyperkeratosis, impaired regeneration, atrophy, or other injurious reactions, resulting in various disease entities. The use of personal devices, activities, occupations, weight bearing, and even unintentional object contact and postures are potential scenarios that account for the development of pressure-related skin disorders. The spectrum of these skin disorders may involve the epidermis (keratinocytes and melanocytes), hair follicles, eccrine glands, nail apparatuses, dermis (fibroblasts, mast cells, and vasculature), subcutis, and fascia. Clarifying the clinical context of each patient and recognizing how pressure at the cellular and tissue levels leads to skin lesions can enhance our comprehension of pressure-related skin disorders to attain better management.

Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders.

The uc.291 transcript controls keratinocytes differentiation by physical interaction with ACTL6A and subsequent induction of transcription of the genes belonging to the epidermal differentiation complex (EDC). Uc.291 is also implicated in the dedifferentiation phenotype seen in poorly differentiated cutaneous squamous cell carcinomas. Here, we would like to investigate the contribution of uc.291 to the unbalanced differentiation state of keratinocytes observed in hyperproliferative skin disorders, e. g., psoriasis. Psoriasis is a multifactorial inflammatory disease, caused by alteration of keratinocytes homeostasis. The imbalanced differentiation state, triggered by the infiltration of immune cells, represents one of the events responsible for this pathology. In the present work, we explore the role of uc.291 and its interactor ACTL6A in psoriasis skin, using quantitative real-time PCR (RT-qPCR), immunohistochemistry and bioinformatic analysis of publicly available datasets. Our data suggest that the expression of the uc.291 and of EDC genes loricrin and filaggrin (LOR, FLG) is reduced in lesional skin compared to nonlesional skin of psoriatic patients; conversely, the mRNA and protein level of ACTL6A are up-regulated. Furthermore, we provide evidence that the expression of uc.291, FLG and LOR is reduced, while ACTL6A mRNA is up-regulated, in an in vitro psoriasis-like model obtained by treating differentiated keratinocytes with interleukin 22 (IL-22). Furthermore, analysis of a publicly available dataset of human epidermal keratinocytes treated with IL-22 (GSE7216) confirmed our in vitro results. Taken together, our data reveal a novel role of uc.291 and its functional axis with ACTL6A in psoriasis disorder and a proof of concept that biological inhibition of this molecular axis could have a potential pharmacological effect against psoriasis and, in general, in skin diseases with a suppressed differentiation programme.

Melanoma and CLL co-occurrence and survival: role of KC history.

BACKGROUND: Survival following melanoma and chronic lymphocytic leukemia (CLL) have both been individually associated with previous history of non-melanoma skin cancers (specifically keratinocyte carcinomas [KC]). Furthermore, melanoma and CLL have been reported to occur within the same patients. The survival experience of patients with both cancers is understudied, and the role of history of KC is unknown. Additional research is needed to tease apart the independent associations between KC and CLL survival, KC and melanoma survival, and the co-occurrence of all three cancers. METHODS: A retrospective cohort study was conducted among patients who were diagnosed with melanoma and/or CLL at a comprehensive cancer center between 2008 and 2020. Multivariable Cox regression models were used to examine the association between history of KC and survival following melanoma and/or CLL with careful consideration of calendar year of diagnosis, treatment regimens and other risk factors. A nested case-control study comparing patients with both CLL and melanoma to those with only CLL or only melanoma was conducted to compare blood parameters across the three groups. RESULTS: A time-dependent association was observed between history of KC and favorable melanoma survival within 4 years following diagnosis and poorer survival post 7 years after melanoma diagnosis. History of KC was not significantly associated with survival following the diagnosis of CLL, after adjustment for clinical factors including historical/concurrent melanoma. Patients with co-occurring melanoma and CLL tended to be diagnosed with melanoma first and had elevated blood parameters including white blood cell and lymphocyte counts as compared with patients who were diagnosed with only melanoma. CONCLUSIONS: History of KC was an independent predictor of survival following melanoma but not of CLL. Additional studies are needed to determine if blood parameters obtained at the time of melanoma diagnosis could be used as a cost-effective way to identify those at high risk of asymptomatic CLL for the promotion of earlier CLL diagnosis.

Non-Coding RNAs as Potential Targets for Diagnosis and Treatment of Oral Lichen Planus: A Narrative Review.

Oral lichen planus (OLP) is a chronic inflammatory disease that is characterized by the infiltration of T cells into the oral mucosa, causing the apoptosis of basal keratinocytes. OLP is a multifactorial disease of unknown etiology and is not solely caused by the malfunction of a single key gene but rather by various intracellular and extracellular factors. Non-coding RNAs play a critical role in immunological homeostasis and inflammatory response and are found in all cell types and bodily fluids, and their expression is closely regulated to preserve normal physiologies. The dysregulation of non-coding RNAs may be highly implicated in the onset and progression of diverse inflammatory disorders, including OLP. This narrative review summarizes the role of non-coding RNAs in molecular and cellular changes in the oral epithelium during OLP pathogenesis.