Expression of RIPK1 and FADD are associated with chemosensitivity and survival in head and heck squamous cell carcinoma via tanshinone IIA-mediated modulation of the RIPK1-FADD-Caspase 8 complex.

Tanshinone IIA (Tan IIA), a main active ingredient of salvia miltiorrhiza, has a wide range of antitumor effects, while its specific role and mechanism in head and neck squamous cell carcinomas (HNSCC) is not fully understood. Totally 59 primary HNSCC patients underwent two courses of induction chemotherapy before surgery. The association between expression of Fas-Associated Death Domain (FADD) and receptor interacting protein kinase 1 (RIPK1) and chemotherapy resistance and survival were evaluated. The cell counting kit-8 was used to detect the effect of Tan IIA on the activity of cisplatin in chemoresistant HNSCC cells through a series of in vitro experiments. The quantitative real-time reverse-transcription polymerase chain reaction, Western blot analysis and flow cytometry were used. FADD and RIPK1 expressions were differentially expressed in Chemosensitive and drug-resistant patients. Furthermore, patients with tumors exhibiting high expression of FADD and RIPK1 had significantly greater risk for chemoresistance and mortality than patients with tumors that had low levels of these proteins. Moreover, Tan IIA reduced the expression of RIPK1 and FADD in HNSCC chemoresistant cell lines, which could increase the chemosensitivity of cisplatin and promote apoptosis. Overexpression of RIPK1 led to attenuation of therapeutic effects of Tan IIA, which were mainly realized through regulation of the RIPK1-FADD-Caspase 8 complex. This study is the first to demonstrate the clinical value and role of FADD and RIPK1 in the treatment of HNSCC. This work establishes the proapoptotic effects of Tan IIA and its potential to enhance chemosensitivity in HNSCC by modulating the RIPK1-FADD-Caspase 8 complex.

Hsa_circ_0058129 regulates papillary thyroid cancer development via miR-873-5p/follistatin-like 1 axis.

BACKGROUND: Papillary thyroid cancer (PTC) is an endocrine malignancy with a high incidence. Circular RNAs (circRNAs) participate in regulating PTC. Here, we analyzed the role of hsa_circ_0058129 (circ_0058129) in PTC. METHODS: The expression of circ_0058129, fibronectin 1 (FN1) mRNA, microRNA-873-5p (miR-873-5p), and follistatin-like 1 (FSTL1) was detected by qRT-PCR and western blot. Cell proliferation was analyzed by CCK-8, EdU, and flow cytometry analysis assays. Cell migration and invasion were evaluated by Transwell assay. The targeting relationship of miR-873-5p and circ_0058129 or FSTL1 was identified through dual-luciferase reporter assay, RIP assay, and RNA pull-down assay. Xenograft mouse model assay was implemented to determine the effect of circ_0058129 on tumor formation in vivo. RESULTS: The circ_0058129 and FSTL1 abundances were increased, while the miR-873-5p content was decreased in PTC tissues and cells compared with control groups. Circ_0058129 shortage inhibited PTC cell proliferation, migration, and invasion. Moreover, miR-873-5p repressed PTC cell malignancy by binding to FSTL1. Circ_0058129 targeted miR-873-5p to regulate FSTL1. CONCLUSION: Circ_0058129 expedited PTC progression through the miR-873-5p/FSTL1 pathway.

Knockdown of lncRNA NEAT1 suppresses hypoxia-induced migration, invasion and glycolysis in anaplastic thyroid carcinoma cells through regulation of miR-206 and miR-599.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal malignancies. Long non-coding RNAs (lncRNAs) are being found to play crucial roles in ATC progression. Herein, we focused on the role of nuclear paraspeckle assembly transcript 1 (NEAT1) on ATC progression under hypoxia and underlying mechanisms governing it. METHODS: The expression levels of NEAT1, miR-206 and miR-599 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell migration and invasion abilities were detected using transwell assays. Glucose consumption and lactate production were determined using a corresponding commercial assay kit. Western blot was performed to evaluate the level of hexokinase 2 (HK2). The targeted interplays between NEAT1 and miR-206 or miR-599 were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model was established to observe the effect of NEAT1 on tumor growth in vivo. RESULTS: Our data indicated that NEAT1 was highly expressed in ATC tissues and cells, and hypoxia induced NEAT1 expression in ATC cells. NEAT1 depletion repressed ATC cell migration, invasion and glycolysis under hypoxia. Mechanistically, NEAT1 acted as a molecular sponge of miR-206 and miR-599. Moreover, the repressive effects of NEAT1 knockdown on ATC cell migration, invasion and glycolysis under hypoxia were mediated by miR-206 or miR-599. Additionally, NEAT1 knockdown weakened tumor growth in vivo. CONCLUSION: In conclusion, our study suggested that a low NEAT1 expression suppressed the migration, invasion, and glycolysis in ATC cells under hypoxia at least partially through modulating miR-206 and miR-599, providing new therapeutic strategies for ATC treatment.

[Prognostic analysis of 76 cases with adenoid cystic carcinoma in salivary gland].

OBJECTIVE: To investigate the prognosis of adenoid cystic carcinoma (ACC) in salivary gland and its influencing factors. METHODS: Clinical and following-up data of 76 patients with ACC in salivary glands were reviewed. Major gland tumors represented 35.5% whereas minor gland tumors comprised 64.5% of the cohort, with 8 cases (10.5%) in stage I, 23 (30.3%) in stage II, 18 (23.7%) in stage III and 27(35.5%) in stage IV. Survival rates were calculated by Kaplan-Merier method. Cumulative survival curves were evaluated using the Log-rank test. Multivariate analysis was performed by Cox proportional hazard model. RESULTS: The regional recurrence rate was 28.9% and distant metastasis rate was 21.1%. The overall 5-year survival rate, tumor-free survival rate and tumor-related survival rate were 73.7%, 61.8% and 74.9% respectively. The overall 10-year survival rate, tumor-free survival rate and tumor-related survival rate were 48.2%, 39.8% and 56.2% respectively. Univariate survival analysis showed pathological type, clinical stage and perineural invasion were relevant to the prognosis of ACC and multivariate analysis showed they were the independent prognostic factors of ACC in salivary gland. CONCLUSIONS: Clinical stage, pathological type and perineural invasion were the independent prognostic factors for adenoid cystic carcinoma in salivary gland. Surgery was the first choice for the treatment of adenoid cystic carcinoma in salivary gland, and postoperative radiotherapy may prolong the tumor-free survival time of patients in stage III and IV.