BackgroundCancer-associated fibroblasts (CAFs) play an important role in regulating tumor progression by transferring exosomes to neighboring cells. Our aim was to clarify the role of microRNA encapsulated in the exosomes derived from CAFs in oral squamous cell carcinoma (OSCC).MethodsWe examined the microRNA expression profiles of exosomes derived from CAFs and donor-matched normal fibroblasts (NFs) from patients with OSCC. We used confocal microscopy to examine the transportation of exosomal miR-34a-5p between CAFs and OSCC cells. Next, luciferase reporter and its mutant plasmids were used to confirm direct target gene of miR-34a-5p. Phenotypic assays and in vivo tumor growth experiments were used to investigate the functional significance of exosomal miR-34a-5p.FindingsWe found that the expression of miR-34a-5p in CAF-derived exosomes was significantly reduced, and fibroblasts could transfer exosomal miR-34a-5p to OSCC cells. In xenograft experiments, miR-34a-5p overexpression in CAFs could inhibit the tumorigenesis of OSCC cells. We further revealed that miR-34a-5p binds to its direct downstream target AXL to suppress OSCC cell proliferation and metastasis. Stable ectopic expression of AXL in OSCC cells overexpressing miR-34a-5p restored proliferation and motility abolished by the miRNA. The miR-34a-5p/AXL axis promoted OSCC progression via the AKT/GSK-3β/β-catenin signaling pathway, which could induce the epithelial-mesenchymal transition (EMT) to promote cancer cells metastasis. The miR-34a-5p/AXL axis enhanced nuclear translocation of β-catenin and then induced transcriptional upregulation of SNAIL, which in turn activated both MMP-2 and MMP-9.InterpretationThe miR-34a-5p/AXL axis confers aggressiveness in oral cancer cells through the AKT/GSK-3β/β-catenin/Snail signaling cascade and might represent a therapeutic target for OSCC.FundNational Natural Science Foundation of China.
Inflammation and desmoplasia are frequently identified in the tumor microenvironment, and have been demonstrated to be effective modulators of malignant biological events. However, the mechanisms by which the inflammatory microenvironment and interstitial fibrosis interact with one another remain to be elucidated. The present study aimed to investigate the degree of inflammation and interstitial fibrosis in tongue squamous cell carcinoma (TSCC), and how this acts to affect the outcome of TSCC. Tissue samples from 93 cases of TSCC and paired tumor-adjacent non-neoplastic tongue epithelium, as well as 14 cases of epithelial dysplasia, were used. Interstitial collagen fibers were assessed using Masson's trichrome stain. Immunohistochemical identification of cancer-associated fibroblasts (CAFs) and stroma-infiltrating B cells was performed via detection of α-smooth muscle actin (SMA), vimentin, desmin and cluster of differentiation 19 (CD19). The clinicopathological significance and overall survival of the TSCC patients were statistically analyzed. Regularly distributed CAFs and CD19+ B cells were identified in the TSCC stroma, whereas no CAFs or CD19+ B cells were observed in epithelial dysplasia samples or paired tumor-adjacent non-neoplastic tongue epithelium samples. The distribution of interstitial collagen fibers and CAFs was closely associated with the tumor stage of the primary cancer, and high levels of CD19+ B cells together with low CAF infiltration were identified to be associated with favorable prognosis in TSCC. In conclusion, the inflammatory and interstitial fibrotic microenvironments coexist in TSCC, and each has specific effects on disease outcome, individually or perhaps collectively. However, it remains to be determined exactly how the microenvironments affect one another in TSCC.
To describe neurosensory dysfunctions, including hyposmia, hypogeusia, and tinnitus, in patients with COVID-19. Methods: Clinical characteristics and oropharyngeal swabs were obtained from 86 patients with COVID-19 hospitalized in Guangzhou Eighth People's Hospital. The chronological analysis method was used to detail neurosensory dysfunction. The cycle threshold (Ct) values were used to approximately indicate viral load. Results: Forty-four (51.2%) patients had neurosensory dysfunction: hyposmia (34, 39.5%), hypogeusia (33, 38.4%), and tinnitus (three, 3.5%). Neurosensory dysfunction was significantly more common in patients under 40 years old (p = 0.001) and women (p = 0.006). Hyposmia and hypogeusia coexisted in 23 (26.7%) patients. The interval between onset of hyposmia and hypogeusia was 0.7 AE 1.46 days. The interval from onset of hyposmia and hypogeusia to typical COVID-19 symptoms was 0.22 AE 4.57 and 0.75 AE 6.77 days; the interval from onset of hyposmia and hypogeusia to admission was 6.06 AE 6.68 and 5.76 AE 7.68 days; and the duration of hyposmia and hypogeusia was 9.09 AE 5.74 and 7.12 AE 4.66 days, respectively. The viral load was high following symptoms onset, peaked within the first week, and gradually declined. Conclusions: Neurosensory dysfunction tends to occur in the early stage of COVID-19, and it could be used as a marker for the early diagnosis of COVID-19.
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