Search

Abstract The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC.

Abstract Long non-coding RNAs (LncRNAs) are implicated in malignant progression of human cancers. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known lncRNA, has been reported to play crucial roles in multiple malignancies including head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of MALAT1 in HNSCC progression remain to be further investigated. Here, we elucidated that compared with normal squamous epithelium, MALAT1 was notably upregulated in HNSCC tissues, especially in which was poorly differentiated or with lymph nodes metastasis. Moreover, elevated MALAT1 predicted unfavorable prognosis of HNSCC patients. The results of in vitro and in vivo assays showed that targeting MALAT1 could significantly weaken the capacities of proliferation and metastasis in HNSCC. Mechanistically, MALAT1 inhibited von Hippel–Lindau tumor suppressor (VHL) by activating EZH2/STAT3/Akt axis, then promoted the stabilization and activation of β-catenin and NF-κB which could play crucial roles in HNSCC growth and metastasis. In conclusion, our findings reveal a novel mechanism for malignant progression of HNSCC and suggest that MALAT1 might be a promising therapeutic target for HNSCC treatment.

ObjectiveWe analysed the diagnostic performance of thyroglobulin in fine-needle aspiration (FNA-Tg) in the suspicious lateral cervical lymph nodes (CLNs) in patients with papillary thyroid cancer (PTC), proposed the best cutoff value and discussed the factors that may affect the diagnostic value of FNA-Tg.MethodsIn the present study, a retrospective analysis of 403 patients with PTC with 448 suspected lateral CLNs metastasis from October 2019 to May 2021 was performed. The cutoff value according to the receiver operating characteristic (ROC) curve was determined, and the Wilcoxon rank-sum test was used to evaluate the correlation between FNA-Tg and factors.ResultsAccording to the ROC curve, the cutoff value of FNA-Tg was 3.69 ng/ml (sensitivity, 92.48%; specificity, 75.00%). Patients who underwent total thyroidectomy were excluded. Compared with US and FNAC, the diagnostic performance of FNA-Tg was the greatest, especially for small CLNs (diameter ≤ 1 cm), cystic CLNs, and patients with Hashimoto’s thyroiditis (HT). Moreover, FNA-Tg levels were correlated with the presence of HT (p = 0.003), the anti-thyroglobulin antibody (Tg-Ab) (p < 0.001), the ratio of metastatic lateral CLNs (p = 0.004) and Tg assay kits (p < 0.001).ConclusionsFNA-Tg measurement is sensitive enough for diagnosing lateral CLN metastases from PTC, but its diagnostic value is compromised by a number of factors.

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.