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Background: Recent studies have shown aberrant expression of micro-RNAs in cancer-associated fibroblasts (CAFs). This study aimed to investigate miR-138 dysregulation in CAFs in oral squamous cell carcinoma (OSCC) and its effects on their phenotype and invasion of adjacent OSCC cells., Methods: Expression of miR-138 was first investigated in OSCC lesions ( n = 53) and OSCC-derived CAFs ( n = 15). MiR-138 mimics and inhibitors were used to functionally investigate the role of miR-138 on CAF phenotype and the resulting change in their ability to support OSCC invasion., Results: Expression of miR-138 showed marked heterogeneity in both OSCC tissues and cultured fibroblasts. Ectopic miR-138 expression reduced fibroblasts' motility and collagen contraction ability and suppressed invasion of suprajacent OSCC cells, while its inhibition resulted in the opposite outcome. Transcript and protein examination after modulation of miR-138 expression showed changes in CAF phenotype-specific molecules, focal adhesion kinase axis, and TGFβ1 signaling pathway., Conclusions: Despite its heterogeneous expression, miR-138 in OSCC-derived CAFs exhibits a tumor-suppressive function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rajthala, Parajuli, Dongre, Ljøkjel, Hoven, Kvalheim, Lybak, Neppelberg, Sapkota, Johannessen and Costea.)

Background: Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). Methodology: CAF and normal oral fibroblasts (NOFs) were isolated from biopsies of OSCC patients and healthy individuals after informed consent and grown in 3D collagen gels. Total RNA was extracted. Global miR expression was profiled using Illumina version 2 panels. The functional impact of altered miR-204 expression in fibroblasts on their phenotype and molecular profile was investigated using mimics and inhibitors of miR-204. Further, the impact of miR-204 expression in fibroblasts on invasion of adjacent OSCC cells was assessed in 3D-organotypic co-cultures. Results: Unsupervised hierarchical clustering for global miR expression resulted in separate clusters for CAF and NOF. SAM analysis identified differential expression of twelve miRs between CAF and NOF. Modulation of miR-204 expression did not affect fibroblast cell proliferation, but resulted in changes in the motility phenotype, expression of various motility-related molecules, and invasion of the adjacent OSCC cells. 3' UTR miR target reporter assay showed ITGA11 to be a direct target of miR-204. Conclusions: This study identifies differentially expressed miRs in stromal fibroblasts of OSCC lesions compared with normal oral mucosa and it reveals that one of the significantly downregulated miRs in CAF, miR-204, has a tumor-suppressive function through inhibition of fibroblast migration by modulating the expression of several different molecules in addition to directly targeting ITGA11.

Background: The aim of the present study was to explore the relationship between excessive daytime sleepiness (EDS), Peak Nasal Inspiratory Flow (PNIF), and patient reported symptoms from the nose., Methology: Six hundred and fifty one consecutive patients referred to a hospital on suspicion of sleep related breathing disorder (SRBD) were included in the study. Daytime sleepiness was assessed by Epworth Sleepiness Scale (EpSS). Nasal airflow was measured with Peak Nasal Inspiratory Flow (PNIF). Symptoms of sino-nasal dysfunction and diseases were graded on Visual Analogue Scales (VAS)., Results: EpSS score was not correlated with nasal flow as measured by PNIF or nasal obstruction - VAS scores. There were significant associations between daytime sleepiness and patient-reported VAS-scores on nasal discharge, headache, coughing, general health and to some extent sneezing when age, gender, BMI and reported co-morbidity levels were adjusted for., Conclusion: A clinical implication of this is that patients with EDS may be evaluated and treated for sino-nasal disease, while medical and surgical measures to open the nose per se may not be effective therapeutic options. A scientific implication is that the relationship between SRBD and sino-nasal disease should be further investigated.