Long Noncoding RNA HOXA-AS2 Promotes Papillary Thyroid Cancer Progression by Regulating miR-520c-3p/S100A4 Pathway.

BACKGROUND/AIMS: Thyroid cancer is one of the most prevalent endocrine tumors. The present study examined the effects of lncRNA HOXA cluster antisense RNA2 (HOXA-AS2) on the progression of papillary thyroid cancer (PTC), and explored the underlying molecular mechanisms. METHODS: Quantitative real-time PCR was used to detect HOXA-AS2, miR-520c-3p and S100 calcium-binding protein A4 (S100A4) expression. Furthermore, the effects of HOXA-AS2 silencing and overexpression on cell proliferation, migration, and invasion were assessed in PTC in vitro by CCK8 and transwell assay. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOXA-AS2 and miR-520c-3p in PTC. RESULTS: We observed that HOXA-AS2 was up-regulated in PTC tissues. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited cell growth in PTC in vitro and in vivo. Further functional assays indicated that HOXA-AS2 significantly promoted PTC cell migration and invasion by promoting EMT. Bioinformatics online programs predicted that HOXA-AS2 sponge miR-520c-3p at 3'-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOXA-AS2 could negatively regulate the expression of miR-520c-3p in PTC cells. MiR-520c-3p was down-regulated in PTC tissues, and S100A4 was predicted as a downstream target of miR-520c-3p, which was confirmed by luciferase reporter assay. CONCLUSION: In summary, our results suggested that the HOXA-AS2/miR-520c-3p/S100A4 axis may play an important role in the regulation of PTC progression, which provides us with new insights into understanding the PTC.

Behaviors and kinetics of toluene adsorption-desorption on activated carbons with varying pore structure.

This work was undertaken to investigate the behaviors and kinetics of toluene adsorption and desorption on activated carbons with varying pore structure. Five kinds of activated carbon from different raw materials were selected. Adsorption isotherms and breakthrough curves for toluene were measured. Langmuir and Freundlich equations were fitted to the equilibrium data, and the Freundlich equation was more suitable for simulating toluene adsorption. The process consisted of monolayer, multilayer and partial active site adsorption types. The effect of the pore structure of the activated carbons on toluene adsorption capacity was investigated. The quasi-first-order model was more suitable for describing the process than the quasi-second-order model. The adsorption data was also modeled by the internal particle diffusion model and it was found that the adsorption process could be divided into three stages. In the external surface adsorption process, the rate depended on the specific surface area. During the particle diffusion stage, pore structure and volume were the main factors affecting adsorption rate. In the final equilibrium stage, the rate was determined by the ratio of meso- and macro-pores to total pore volume. The rate over the whole adsorption process was dominated by the toluene concentration. The desorption behavior of toluene on activated carbons was investigated, and the process was divided into heat and mass transfer parts corresponding to emission and diffusion mechanisms, respectively. Physical adsorption played the main role during the adsorption process.

Hypoxia-induced NIPP1 activation enhances metastatic potential and predicts poor prognosis in hepatocellular carcinoma.

Hypoxia is known to promote hepatocellular carcinoma (HCC) invasion and metastasis and nuclear inhibitor of protein phosphatase 1 (NIPP1) overexpression contributes to the malignant phenotype in HCC. The aim of this study was to investigate the role of NIPP1 in HCC development under hypoxia. We first conducted a study with 106 cases to explore the association of NIPP1 and/or enhancer of zeste homolog 2 (EZH2) expression with poor prognosis in HCC. Then additional 352 independent cases were recruited to validate the results in the first stage. Hypoxia was induced by culturing HCC cells in 1 % O2 or of the treatment with hypoxic agent. The expression levels of NIPP1/EZH2 in both HCC tissues and HCC cell lines were detected by RT-PCR, Western blot, or immunohistochemistry. We also studied the effects of the loss of function of NIPP1 and EZH2 on malignant phenotypes, downstream pathway, and inflammatory factors activities using gene silencing strategy. Overall, we found that NIPP1 and EZH2 were overexpressed in both HCC tissue samples and HCC cell lines. High expression of HIPP1 was associated with poor prognosis and clinicopathological features in patients with advanced HCC. HIPP1 expression positively correlated with the expression of hypoxia marker (carbonic anhydrase IX). Hypoxia induced high expression of NIPP1. NIPP1/EZH2 knockdown in HCC cell lines under hypoxia suppressed the malignant phenotypes, reduced the expression of hypoxia-inducible Factor 1α, downstream molecules of EZH2, and inhibit the activity of inflammatory factors. In conclusion, we found that NIPP1 could be activated by hypoxia and contributed to hypoxia-induced invasive and metastatic potential in HCC.

[A case of retroperitoneal Castleman's disease with paraneoplastic pemphigus].

Paraneoplastic pemphigus is a rare autoimmune bullous dermatosis, which is caused by potential neoplasm, especially the Castleman's disease. Castleman's disease associated with paraneoplastic pemphigus is misdiagnosed frequently and easily in clinical practices. Furthermore, it is reported that the mortality rate for this disease is very high. Bronchiolitis obliterans is the most common complication and the most important cause of death. There was a female patient presenting recalcitrant mucocutaneous erosions, ulcers and scattered erythemas in the body. The patient was diagnosed and treated for pemphigus vulgaris with little success in Xiangya Hospital, Central South University in January 2015. Further investigations confirmed the diagnosis of paraneoplastic pemphigus with retroperitoneal tumor. Subsequently, the patient was treated with tumor resection in combination with intravenous immunoglobulin and corticosteroids. The pathology revealed that it was the Castleman's disease. Her mucocutaneous performance recovered obviously and the bronchiolitis obliteran did not appear in the follow-up. Castleman's disease associated with paraneoplastic pemphigus should be considered when mucosal and skin lesions showing no improvement under corticosteroids. Early and complete removal of the tumor together with immunotherapy could be beneficial to the patient's prognosis.

[Research progress in poorly differentiated thyroid carcinoma].

Poorly differentiated thyroid carcinoma (PDTC) is a special type of thyroid carcinoma, the morphology and biological behavior of which are between well-differentiated and undifferentiated (anaplastic) carcinomas. Currently, the diagnosis of PDTC mainly relies on the pathological standards. Although "Turin standards" is commonly used, there is no generally accepted diagnostic criteria. Surgery is still the main treatment for PDTC, but the adjuvant therapies are in dispute. Age, tumor node metastasis (TNM) stage and integrity of surgical of PDTC are major factors that affect the prognosis. The identification of eosinophilic phenotype (hurthle cells) of PDTC is important. Some common immunohistochemical and molecular biomarkers, such as the insulin-like growth factor II mRNA-binding protein 3 (IMP3), E-cadherin and proliferating protein Ki67, may be helpful for distinguishing PDTC from other thyroid carcinoma. With the progress in studies regarding molecular markers for PDTC and the clinical characters of PDTC patients with large samples, the diagnosis for PDTC will greatly improved and the pathogenesis for PDTC will be elucidated.

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21.

Background: The long noncoding RNA (lncRNA) functions as a regulator of initiation, progression, and metastasis of thyroid carcinomas. lncRNA OTUD6B antisense RNA 1 (OTUD6B-AS1) is a tumor-suppressive noncoding RNA in clear cell renal cell carcinoma. The role of OTUD6B-AS1 in thyroid carcinomas has not been reported yet. We aim to investigate the expression and biological functions of OTUD6B-AS1 in thyroid carcinomas. Methods: The expression level of OTUD6B-AS1 was measured in 60 paired human thyroid carcinoma tissues and corresponding adjacent normal thyroid tissues. The correlations between the OTUD6B-AS1 expression levels and clinicopathological features were evaluated using the Mann-Whitney test. The effects of OTUD6B-AS1 on thyroid carcinoma cells were determined via the MTT and transwell assays. The potential targets of OTUD6B-AS1 were screened using the online programs OncomiR and StarBase 3.0, and the LncBase Predicted v.2. Luciferase reporter assay was used to confirm the interactions between OTUD6B-AS1 and its potential targets. Results: OTUD6B-AS1 was downregulated in thyroid carcinoma tissue samples. The expression of OTUD6B-AS1 correlated with tumor size, clinical stage, and lymphatic metastasis of thyroid carcinoma. Overexpression of OTUD6B-AS1 significantly decreased the viability, migration, and invasion of thyroid carcinoma cells. Online programs predicted miR-183-5p and miR-21 as potential targets of OTUD6B-AS1. Luciferase reporter assays showed miR-183-5p and miR-21 bound to OTUD6B-AS1. Moreover, overexpression of miR-183-5p and miR-21 compromised the inhibitory effects of OTUD6B-AS1 on viability, migration, and invasion of thyroid carcinoma cells. Conclusions: Taken together, our findings present in vitro evidence of lncRNA OTUD6B-AS1 as a tumor suppressor in thyroid carcinomas. OTUD6B-AS1 inhibits viability, migration, and invasion of thyroid carcinoma by targeting miR-183-5p and miR-21.

Survival and analysis of prognostic factors for hepatoblastoma: based on SEER database.

BACKGROUND: The goal of this study is to assess the newest survival of hepatoblastoma (HB) and the risk factors which impacted on survival by using the Surveillance, Epidemiology and End Results (SEER) database, also calculate the incidence of HB in recent years. METHODS: We calculate age-adjusted incidence of HB by using SEER 21 registries. Age, sex, race, tumor size, macrovascular involvement, multifocal tumor, distant metastasis, the way of treatment, and the survival were collected for survival and analysis of prognostic factors in SEER 18 registries. Survival curves, according to different factors, were obtained by Kaplan-Meier estimates. Multivariable Cox regression models were also built. RESULTS: The overall age-adjusted incidence of HB was 0.19 patients per 100,000 children with a statistically significant increase per year. Overall survival (OS) at 1-, 3- and 5-year for all patients were 89.3%, 84.6%, and 81.9%, respectively. Multivariate analysis showed tumor size >5 cm [hazard ratio (HR), 8.271; 95% confidence interval (CI), 1.134-60.310], multiple tumors (HR, 2.578; 95% CI, 1.424-4.668) and no-surgery treatment (HR, 7.520; 95% CI, 4.121-13.724) were independent indicators of poor prognosis. Only the age ≥2-year-old (HR, 3.240; 95% CI, 1.433-7.326) and multiple tumors (HR, 2.395; 95% CI, 1.057-5.430) were the risk factors for the surgical treatment group. CONCLUSIONS: The survival of patients with HB has been greatly improved in the recent years, and at the same time, due to the application of better chemotherapy, we should re-evaluate the traditional risk indicators of prognosis in order to better apply to the clinical.

LncRNA BC032020 suppresses the survival of human pancreatic ductal adenocarcinoma cells by targeting ZNF451.

This study examined the effects of long non­coding RNA (lncRNA) BC032020 on the development of human pancreatic ductal adenocarcinoma (PDAC), and the potential molecular mechanisms responsible for these effects. The expression of BC032020 was assessed in 20 pairs of PDAC tumor tissues and adjacent normal tissues. The overexpression of BC032020 was enforced in the AsPC­1 and PANC­1 cells, and the effects on cell proliferation, cell cycle distribution, cell migration and apoptosis were determined. We also analyzed the functions of zinc finger protein 451 (ZNF451), which shares a gene sequence with two exons of BC032020 and a non­coding region with another two exons, in PDAC cells. The AsPC­1 and PANC­1 cells that overexpressed BC032020 were used to establish a subcutaneous tumor xenograft model in order to examine the effects of BC032020 on tumor growth in vivo. The results revealed that the BC032020 levels in the PDAC tumor tissues were lower than those in the adjacent normal tissues, and ZNF451 expression inversely correlated with the BC032020 levels in the PDAC tumor tissues and cell lines. BC032020 overexpression led to a decrease in ZNF451 expression; it also suppressed the proliferation and migration of the AsPC­1 and PANC­1 cells, and induced G1 phase arrest and cell apoptosis. The results of in vivo experiments revealed that BC032020 suppressed tumor growth in a xenograft model by inhibiting ZNF451 expression. Taken together, the findings of this study indicate that BC032020 suppresses the survival of PDAC cells by inhibiting ZNF451 expression.

Concurrent occurrence of primary hepatocellular and cholangiocellular carcinoma in the different part of the liver: a case report.

Combined hepatocellular-cholangiocarcinoma which shows features of both hepatocellular and biliary epithelial differentiation is a rare form of primary liver cancer. The rarer is that the two types of cancer occur in the different lobe of the same liver concurrently.