Micro RNAs (miRNAs) have a key role in gene expression regulation in cancer. The aim of the current study is to evaluate the prognostic value of miR-34b/c promoter hypermethylation, gene expression, and polymorphism in HPV-negative oral squamous cell carcinomas (OSCC). MiR-34b/c promoter hypermethylation and pre-miR-34b/c polymorphism rs4938723 were evaluated in tumor tissues of 148 patients, and miR-34b expression in 123 HPV-negative OSCC. For risk assessment, the control group was comprised of 175 healthy individuals. MiR-34b/c promoter hypermethylation was determined by methylation-specific PCR. Gene expression, genotyping and HPV screening was assessed by Q-PCR. The data from our hospital cohort indicated that miR-34b/c DNA methylation was associated with nodal status (p = 0.048), and predicted the shorter overall survival of HPV-negative OSCC patients (p = 0.008). Down-regulated miR-34b/c expression was associated with smoking (p = 0.047), alcohol use (p = 0.009), stage (p = 0.025), recurrences (p = 0.000), and a poor survival (p = 0.00029). Median values of miR-34b expression were significantly lower in advanced stages III/IV as opposed to stage I/II, p = 0.006, and in nodal positive vs negative patients (p = 0.045). TCGA data also indicated that tumors with stage I–III expressed significantly higher levels of miR-34b, compared to tumors with stage IV (p = 0.035), Low miR-34b/c expression was associated with poor survival in smokers (p = 0.001) and patients with tongue carcinomas (p = 0.00003), and TCGA analysis confirmed these findings although miR-34b expression and miR-34b/c methylation were not associated with survival outcome in the whole TCGA cohort. A significant negative miR-34b/c expression–methylation correlation was observed in our hospital cohort (p = 0.017) and in TCGA cohort. Pre-miR-34b/c polymorphism was not associated with oral cancer risk. Our findings indicate that miR-34b/c hypermethylation and low miR-34b expression could promote the progression and predict the poor prognosis for HPV-negative OSCC, which suggests miR-34b/c as a promising biomarker and therapeutic target for OSCC in the future.

Osteoarthritis (OA) is a progressive degenerative disease that affects all synovial joints, causing the disability of the main locomotor diarthrodial joints. OA pathogenesis is caused by a complex interplay between a number of genetic and environmental risk factors, involved in the early onset and progression of this chronic inflammatory joint disease. Uncovering the underlying immunological and genetic mechanisms will enable an insight into OA pathophysiology and lead to novel and integrative approaches in the treatment of OA patients, together with a reduction of the disease risk, or a delay of its onset in susceptible patients.

Osteoarthritis (OA) is a progressive inflammatory disease of synovial joints and a leading cause of disability among adults. Inflammation-related genes, including genes for Toll-like receptors (TLRs), are tightly controlled by several microRNAs that, in addition to their pivotal role in the epigenetic regulation of target genes, are ligands for TLR activation and downstream signaling. Thus, we evaluated the association between OA risk and genetic variants in TLR2, TLR3, TLR4, TLR7, TLR9, and microRNAs that regulate TLRs signaling miR146a, miR155, and miR196a2. Our study group consisted of 95 surgically treated OA patients and a control group of 104 healthy individuals. Genetic polymorphisms were determined using TaqMan real-time PCR assays (Applied Biosystems). Adjusted logistic regression analysis demonstrated that polymorphisms in TLR4 rs4986790 (OR = 2.964, p = 0.006), TLR4 rs4986791 (OR = 8.766, p = 0.00001), and TLR7 rs385389 (OR = 1.579, p = 0.012) increased OA risk, while miR-196a2 rs11614913 (OR = 0.619, p = 0.034) was significantly associated with decreased OA risk. Our findings indicate that polymorphisms in the TLR4 and TLR7 genes might increase OA risk and suggest a novel association of miR-196a2 polymorphism with decreased OA susceptibility. The modulation of TLRs and miRNAs and their cross-talk might be an attractive target for a personalized approach to OA management.

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Vitamin D receptor (VDR) gene polymorphisms could play a significant role in the susceptibility and pathogenesis of osteoarthritis (OA), the most common degenerative joint disorder in humans. The current study involved 94 OA patients and 100 healthy, asymptomatic controls. VDR variants FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232) and EcoRV (rs4516035) were genotyped using TaqMan-based real-time PCR. Adjusted odds ratio (OR) analysis showed that VDR TaqI and FokI polymorphisms are significantly associated with susceptibility to OA (OR=1.986, P=0.001 and OR=1.561, P=0.017, respectively). Joint-specific analysis showed that the VDR TaqI polymorphism was associated with risk of hip OA (OR=1.930, P=0.005) and knee OA (OR=1.916, P=0.028), while the VDR FokI polymorphism was associated with higher risk of knee OA (OR=2.117, P=0.012). VDR TaqI and FokI polymorphisms are associated with the occurrence of persistent pain (P=0.005 and P=0.027, respectively), while ApaI was associated with a family history of OA (p=0.004). The VDR FokI and TaqI genetic variants significantly contribute to osteoarthritis susceptibility, the occurrence of persistent pain, and potentially to joint-specific OA risk.