CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis.

Circular RNAs (circRNAs) are well-known to exert significant roles in regulating the pathological processes, including human carcinogenesis. Currently, less is known about their exact roles in head and neck squamous cell carcinoma (HNSCC). Herein, we aimed to investigate and validate the role of a novel circRNA, circMAT2B, as well as its potential molecular mechanism in HNSCC progression. A cohort of 41 paired of HNSCC tumor tissues and adjacent normal tissues from HNSCC patients were collected. Further, we characterized circMAT2B expression patterns in HNSCC tissues and cell lines, as well as exploring its association with the prognosis of HNSCC patients. Biological functions on cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8, EdU incorporation, TUNEL, wound healing, and transwell assays. Glutaminolysis was evaluated by measuring glutamine, glutamate, and α-ketoglutarate (α-KG) levels. The regulatory network of circMAT2B/miR-491-5p/ASCT2 axis was verified by RNA immunoprecipitation and luciferase reporter assays. Western blot was conducted to detect the level of ASCT2 and GLS1. Remarkably overexpressed circMAT2B was observed in HNSCC tissues and cell lines, of which high abundance was positively correlated with patients' poor prognosis. Silencing of circMAT2B inhibited cell proliferation, migration, and invasion, as well as glutaminolysis. miR-491-5p, interacted with ASCT2, was identified to be a downstream target of circMAT2B, thereby involving in circMAT2B-mediated biological effects. In summary, we draw a conclusion that circMAT2B could modulate the processes of cell proliferation, migration, invasion, and glutaminolysis of HNSCC cells partly via the miR-491-5p/ASCT2 axis by a molecular mechanism of competing endogenous RNA (ceRNA), implying an underlying circRNA-targeted therapy for HNSCC treatment.

A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis.

Emerging evidence has demonstrated the pivotal roles of circular RNAs (circRNAs) in the modulation of malignancy and pathological progression among multiple human cancers. Glucose metabolism reprogramming is a widely identified characteristic for contributing to facilitate tumorigenesis. Nonetheless, their contributions to head and neck squamous cell carcinoma (HNSCC) cell glycolysis remain to be further elucidated. Herein, we aim to investigate the role of circRNA, hsa_circ_0018180 (also named as circPARD3) in HNSCC. Expression patterns of circPARD3 in HNSCC tissues and different cell lines were determined by qRT-PCR assay, as well as its correlation with the prognosis of survival. CCK-8, EdU incorporation, and transwell assays were carried out to assess the cell viability, proliferation, migration, and invasion, respectively. Glucose uptake and lactate production were evaluated by preforming glycolysis. Mechanistically, the circPARD3/miR-5194/ENO1 axis was verified by RNA immunoprecipitation (RIP) and luciferase reporter assays. Western blot analysis was employed to measure the epithelial-mesenchymal transition (EMT)-associated biomarkers. Upregulated circPARD3 observed in HNSCC tissues and cell lines indicated the poor prognosis of patients. Stable knockdown of circPARD3 dramatically exerted the suppressive effects on cell viability, proliferation, migration, and invasion, as well as glucose uptake and lactate production. Mechanistically, circPARD3 harbored miR-5194, serving as a miRNA sponge, thereby increasing ENO1 expression. Moreover, ENO1 evidently reversed miR-5194-mediated attenuated malignant behaviors. Collectively, our study identified an oncogenic role of circPARD3 in HNSCC through a novel machinery of circPARD3/miR-5194/ENO1 and provided a promising therapeutic target for HNSCC.

Interferon alpha inhibits hepatocellular carcinoma growth through inducing apoptosis and interfering with adhesion of tumor endothelial cells.

The aim of this study was to observe the effect of interferon alpha (IFNalpha) on tumor endothelial cells (TECs) in highly metastatic hepatocellular carcinoma (HCC) model, and to investigate the underlying mechanism. Nude mice with HCC xenograft were treated with IFNalpha. Gene expression profiles of TECs were analyzed by utilizing cDNA microarray. The differentiation of tumor blood vessels was evaluated by CD31/alphaSMA dual immunohistochemistry. Apoptosis of TECs was determined by CD31/TUNEL double staining. The functions of TECs in adhesion and uptake of acetylated low-density lipoprotein were observed in vitro. Results showed that IFNalpha effectively inhibited HCC tumor growth, with decreased microvessel density, increased apoptosis in TECs and normalized tumor blood vessels. cDNA microarray analysis revealed differential gene expression patterns in TECs under the treatment of IFNalpha. The cell-cell contact distribution of VE-Cadherin and uptake of acetylated low-density lipoprotein were significantly inhibited by IFNalpha in cultivated TECs. These results suggest that IFNalpha may induce apoptosis and interfere with hemophilic adhesion of TECs. The changes of gene expression in TECs contribute essentially to its effect of anti-angiogenesis and the subsequent inhibition of tumor progression.

[Influencing factors for intrahepatic distant recurrence of liver cancer after radiofrequency ablation].

OBJECTIVE: To analyze the influencing factors affecting intrahepatic distant recurrence after radiofrequency ablation (RFA) for primary hepatic cancer. METHODS: Eighty patients with primary hepatic tumors underwent RFA treatment between January 2002 and June 2005 were retrospectively analyzed. There were 49 males and 31 females aged from 34 to 84 years old. The tumor size was less than 5 cm and no more than 3 nodules. Univariate analysis and multivariate analysis were used to evaluate the risk factors for intrahepatic distant recurrence after RFA. RESULTS: The cumulative rates of intrahepatic distant recurrence were 6.3%, 32.0%, and 67.3% at 1, 3, and 5 years, respectively. Univariate analysis revealed that pretreatment serum AFP level of >or= 50 microg/L (P = 0.029), decarboxy prothrombin (DCP) level of >or= 40 mAu/ml (P = 0.004), ablative margin of < 1 cm (P = 0.035), prothrombin time activity percent target of < 70% (P = 0.012), and poor Child-Pugh grade (P = 0.002) were related to intrahepatic distant recurrence. A multivariate analysis revealed that pretreatment serum AFP and DCP level, ablative margin and Child-Pugh grade were independent risk factors for intrahepatic distant recurrence. CONCLUSIONS: Primary liver cancer patients with high serum AFP, DCP and poor Child-Pugh grade before RFA should be carefully followed up to monitor any intrahepatic distant recurrence. A sufficient ablative margin in RFA for primary liver cancer is required to prevent recurrence.