The aim of this review is to discuss current findings regarding the roles of miRNAs in periodontal diseases and the potential use of saliva as a diagnostic medium for corresponding miRNA investigations. For periodontal disease, investigations have been restricted to tissue samples and five miRNAs, that is, miR-142-3p, miR-146a, miR-155, miR-203, and miR-223, were repeatedly validated in vivo and in vitro by different validation methods. Particularly noticeable are the small sample sizes, different internal controls, and different case definitions of periodontitis in in vivo studies. Beside of that, the validated miRNAs are associated with inflammation and therefore with various diseases. Furthermore, several studies successfully explored the use of salivary miRNA species for the diagnosis of oral cancer. Different cancer types were investigated and heterogeneous methodology was used; moreover, no overlap of results was found. In conclusion, five miRNAs have consistently been reported for periodontitis; however, their disease specificity, detectability, and expression in saliva and their importance as noninvasive markers are questionable. In principle, a salivary miRNA diagnostic method seems feasible. However, standardized criteria and protocols for preanalytics, measurements, and analysis should be established to obtain comparable results across different studies.

Emerging evidence indicates that microRNAs play a pivotal role in neural remodeling after spinal cord injury (SCI). This study aimed to investigate the mechanisms of miR-135a-5p in regulating the functional recovery of SCI by impacting its target genes and downstream signaling. The gene transfection assay and luciferase reporter assay confirmed the target relationship between miR-135a-5p and its target genes (specificity protein 1 [SP1] and Rho-associated kinase [ROCK]1/2). By establishing the H2O2-induced injury model, miR-135a-5p transfection was found to inhibit the apoptosis of PC12 cells by downregulating the SP1 gene, which subsequently induced downregulation of pro-apoptotic proteins (Bax, cleaved caspase-3) and upregulation of anti-apoptotic protein Bcl-2. By measuring the neurite lengths of PC12 cells, miR-135a-5p transfection was found to promote axon outgrowth by downregulating the ROCK1/2 gene, which subsequently caused upregulation of phosphate protein kinase B (AKT) and phosphate glycogen synthase kinase 3β (GSK3β). Use of the rat SCI models showed that miR-135a-5p could increase the Basso, Beattie, and Bresnahan (BBB) scores, indicating neurological function recovery. In conclusion, the miR-135a-5p-SP1-Bax/Bcl-2/caspase-3 and miR-135a-5p-ROCK-AKT/GSK3β axes are involved in functional recovery of SCI by regulating neural apoptosis and axon regeneration, respectively, and thus can be promising effective therapeutic strategies in SCI.

Long non-coding RNAs (lncRNAs), which may be modulated by chemokines, are key regulators in many cancers including oral squamous cell carcinoma (OSCC). An understanding of lncRNAs involved in chemokine (CC motif) ligand 18 (CCL18)-induced OSCC promotion remains elusive. The present study using lncRNA sequencing found LINC00319 to be significantly upregulated in OSCC cells subjected to rCCL18 stimulation. Furthermore, LINC00319 knockdown was found to attenuate the carcinogenic function of CCL18 in OSCC, reducing OSCC proliferation, metastasis, epithelial-mesenchymal transition (EMT), and angiogenesis. LINC00319 was demonstrated to act as a ceRNA in OSCC, which directly responded to miR-199a-5p and rescued the repression of FZD4 by miR-199a-5p. Functionally, in vitro and in vivo experiments showed that LINC00319 promoted OSCC growth and metastasis via downregulating miR-199a-5p and upregulating FZD4. In vitro rescue assays demonstrated that miR-199a-5p inhibitor or FZD4 overexpression reversed the effects of LINC00319 silencing in OSCC. Importantly, the expression of miR-199a-5p and FZD4 were found to be mediated by CCL18, and miR-199a-5p mimics inhibited the CCL18-promoting effects in oral cancer cells. Taken together, these results evidenced a mechanism of CCL18 action in OSCC mediated through the LINC00319/miR-199a-5p/FZD4 signaling pathway, which may comprise a potential target for OSCC therapeutic development.