Expression Profiling Identifies Circular RNA Signature in Hepatoblastoma.

BACKGROUND/AIMS: Hepatoblastoma is the most common malignant pediatric liver cancer. circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of circRNAs in hepatoblastoma is still unknown. METHODS: Circular RNA microarray was conducted to identify hepatoblastoma-related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in hepatoblastoma. MTT assays, Ki67 staining, and Transwell assays were conducted to clarify the role of circRNA in hepatoblastoma in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in hepatoblastoma cell. RESULTS: 869 differentially expressed circRNAs were identified between hepatoblastoma and adjacent normal liver samples, including 421 up-regulated circRNAs and 448 down-regulated circRNAs. The significant enriched GO term of hepatoblastoma-related circRNAs in biological process, cellular component, and molecular function were "chromosome organization", "cytoplasm", and "organic cyclic compound binding". Tight junction signaling pathway was ranked the Top 1 potentially affected by circRNA-mediated regulatory network. circ_0015756 was significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. circ_0015756 silencing decreased hepatoblastoma cell viability, proliferation, and invasion in vitro. circ_0015756 acted as miR-1250-3p sponge to regulate hepatoblastoma cell function. CONCLUSIONS: circRNAs are involved in the pathogenesis of hepatoblastoma. circ_0015756 is a promising target for the prognosis, diagnosis, and treatment of hepatoblastoma.

Experimental Study on the Performance of Hydraulic Vibration Assisted Broaching (HVAB) Based on Piezoelectric Sensors.

In order to improve the keyway broaching process and verify the feasibility of vibration-assisted broaching process, an experimental study on a novel hydraulic vibration assisted broaching (HVAB) system with double-valve electro-hydraulic exciter (DVEHE) is proposed in this paper. The performances of HVAB at different excitation frequencies were compared from three aspects: (a) the cutting force under the different vibration frequencies, (b) the surface roughness of the workpiece, and (c) the flank face wear of the tool. For precision on-line measurement of larger broaching forces, four piezoelectric sensors were fixed on the broaching machine. The experimental results show that HVAB can effectively improve the performance of the broaching process, approximately reduce the broaching force by as much as 9.7% compared to conventional broaching (CB) and improve the surface quality of workpiece. Some explanations are offered to support the observations.

Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma.

BACKGROUND: Forkhead Box P3 (Foxp3) is a regulatory T cells marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of Foxp3 expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma (OSCC). METHODS: Foxp3 expression was examined using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 273 OSCC patients. Statistical analysis was performed to evaluate the associations between Foxp3 expression, the clinicopathologic characteristics and prognostic factors in OSCC. RESULTS: Foxp3 protein expression was significantly associated with lymph node metastasis (P <0.01). Both univariate and multivariate analyses revealed that Foxp3 was an independent factor for both 5 years overall survival (OS) and relapse-free survival (RFS) (both P <0.01). Patients with Foxp3 overexpression had shorter OS and RFS. CONCLUSIONS: Our results determined that elevated Foxp3 protein expression was a predictive factor of outcome in OSCC and could act as a promising therapeutic target.

Selective Versus Comprehensive Neck Dissection in Patients With T1 and T2 Oral Squamous Cell Carcinoma and cN0pN(+) Neck.

PURPOSE: There is still no consensus on the oncologic safety of selective neck dissection (SND) in the management of pathologically positive neck in patients with oral squamous cell carcinoma (OSCC). This study compared the clinical outcome between SND and comprehensive neck dissection (CND) for patients with T1 and T2 OSCC and a clinically negative but pathologically positive neck. MATERIALS AND METHODS: Retrospective study of medical records of patients with T1 and T2 OSCC and clinical N0 but pathologic N(+) disease from March 2000 through March 2011 was performed. Thirty-seven patients underwent SND or CND. Median follow-up was 51 months. Regional control and disease-specific survival rates were statistically analyzed. RESULTS: No significant differences in 3-year ipsilateral neck control rate (81.8 vs 91.7%; P = .590 by log-rank test) and overall regional control rate (72.7 vs 86.8%; P = .424 by log-rank test) were found between the SND and CND groups. Three-year disease-specific survival rates of the SND and CND groups were 72.7 and 82.1%, respectively. No significant difference was found between these 2 groups by log-rank test (P = .428). CONCLUSIONS: The results indicate that SND in conjunction with postoperative radiotherapy is effective in the management of patients with T1 and T2 OSCC and cN0pN(+) neck.

Tumor Suppressive Role of MUC6 in Wilms Tumor via Autophagy-Dependent ß-Catenin Degradation.

Wilms tumor is the most common renal malignancy in children. Known gene mutations account for about 40% of all wilms tumor cases, but the full map of genetic mutations in wilms tumor is far from clear. Whole genome sequencing and RNA sequencing were performed in 5 pairs of wilms tumor tissues and adjacent normal tissues to figure out important genetic mutations. Gene knock-down, CRISPR-induced mutations were used to investigate their potential effects in cell lines and in-vivo xenografted model. Mutations in seven novel genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) occurred in more than one patient. The most prevalent mutation was found in MUC6, which had 7 somatic exonic variants in 4 patients. In addition, TaqMan assay and immunoblot confirmed that MUC6 expression was reduced in WT tissues when compared with control tissues. Moreover, the results of MUC6 knock-down assay and CRISPR-induced MUC6 mutations showed that MUC6 inhibited tumor aggression via autophagy-dependent ß-catenin degradation while its mutations attenuated tumor-suppressive effects of MUC6. Seven novel mutated genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) were found in WT, among which MUC6 was the most prevalent one. MUC6 acted as a tumor suppressive gene through autophagy dependent ß-catenin pathway.

Single-Cell Characterization of Malignant Phenotypes and Developmental Trajectories of Adrenal Neuroblastoma.

Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.

Long non-coding RNA-CRNDE: a novel regulator of tumor growth and angiogenesis in hepatoblastoma.

Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. They have emerged as key players in the pathology of several tumors, including hepatoblastoma. In this study, we elucidate the biological and clinical significance of CRNDE up-regulation in hepatoblastoma. CRNDE is significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. CRNDE knockdown reduces tumor growth and tumor angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, and angiogenic effect in vitro. Mechanistic studies show that CRNDE knockdown plays its anti-proliferation and anti-angiogenesis role via regulating mammalian target of rapamycin (mTOR) signaling. Taken together, this study reveals a crucial role of CRNDE in the pathology of hepatoblastoma. CRNDE may serve as a promising diagnostic marker and therapeutic target for hepatoblastoma.