Circ-EIF3I Promotes Hepatocellular Carcinoma Progression Through Modulating miR-361-3p/DUSP2 Axis.

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers globally. Circular RNAs (circRNAs) have been implicated in the development of HCC. Previous studies have confirmed that circ-EIF3I plays an important role in the progress of lung cancer. Nevertheless, the biological functions of circ-EIF3I and the underlying mechanisms by which they regulate HCC progression remain unclear. In this study, the regulatory mechanism and targets were studied with bioinformatics analysis, luciferase reporting analysis, transwell migration, Cell Counting Kit-8, and 5-Ethynyl-2'-deoxyuridine analysis. In addition, in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circ-EIF3I in HCC. The result shows that the circ-EIF3I expression was increased in HCC cell line, which means that circ-EIF3I plays a role in the progression of HCC. Downregulation of circ-EIF3I suppressed HCC cells' proliferation and migration in both in vivo and in vitro experiments. Bioinformatics and luciferase report analysis confirmed that both miR-361-3p and Dual-specificity phosphatase 2 (DUSP2) were the downstream target of circ-EIF3I. The overexpression of DUSP2 or inhibition of miR-361-3p restored HCC cells' proliferation and migration ability after silence circ-EIF3I. Taken together, our study found that downregulation of circ-EIF3I suppressed the progression of HCC through miR-361-3p/DUSP2 Axis.

MiR-147a mediated by sodium new houttuyfonate could enhance radiosensitivity of non-small cell lung cancer cells via suppressing STAT3.

BACKGROUND: Radioresistance is a huge obstacle in radiotherapy of non-small cell lung cancer (NSCLC) and how to raise radiosensitivity is an urgent issue. OBJECTIVES: In this study, we investigated the role and molecular mechanism of sodium new houttuyfonate (SNH) in regulation of radiosensitivity of NSCLC cells. MATERIAL AND METHODS: The Cell Counting Kit-8 (CCK-8) was used to measure cell viabilities of NSCLC cell lines A549 and HCC827 after a treatment with SNH (0 mM, 0.1 mM and 0.3 mM). It examined cytotoxicity induced by X-ray (0 Gy, 1 Gy, 2 Gy, 4 Gy, 6 Gy, and 8 Gy) after SNH (0.3 mM) treatment, while flow cytometry was used for apoptosis detection use. Expression of miR-147a or signal transducer and activator of transcription (STAT3) in selected cell lines was assessed through real-time quantitative polymerase chain reaction (RT-qPCR). The CCK-8 was then applied to measure cytotoxicity in cells with miR-147a upregulation or STAT3 suppression under irradiation apoptosis changes were detected with flow cytometry. Thereafter, binding conditions between miR-147a and STAT3 were checked using luciferase reporter assays. Expressions of STAT3 in A549 transfected by siNC, siSTAT3, and by siSTAT3 and miR-147a mimics were checked using RT-qPCR and the phosphorylation of STAT3 was observed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The SNH treatment significantly suppressed cell viabilities and increased apoptosis of lung cancer cells. Cytotoxicity and apoptosis in A549 cells were both enhanced after SNH treatment and raised as the dosages of X-ray grew. MiR-147a presented lower expression in lung cancer cells and was upregulated by SNH, which further contributed to higher cell apoptosis after irradiation. STAT3 directly bound miR-147a and was more expressed in NSCLC cells. Inhibited phosphorylation of STAT3 promoted apoptosis in A549 cells after X-ray exposure. Overexpressed miR-147a inactivated STAT3 signaling, adding to cell apoptosis after irradiation. CONCLUSIONS: SNH-induced miR-147a increased radiosensitivity of A549 cells through inactivation of STAT3 pathway.

Management of primary gastric small cell carcinoma in China.

BACKGROUND: Primary gastric small cell carcinomas (GSCCs) are increasingly identified by endoscopy, and account for 15-20% of all gastric neuroendocrine tumors (NETs). GSCCs have the worst prognosis with the highest rate of metastases. PURPOSE: To provide useful information for clinicians and researchers to better manage patients with GSCC, we studied the clinical features of GSCC and explored the corresponding therapies and prognosis. METHODS: A literature search was conducted through PUBMED, EMBASE, CNKI and WanFang Databases using search terms "stomach" or "gastric" and "small cell carcinoma" or "poorly differentiated neuroendocrine carcinoma", for the period 1999 to 2012. And the cases reported were all from China. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. RESULTS: Two hundred and five eligible cases were analyzed. The median age of patients was 62 years, with a male-to-female ratio of 5.4:1. Of the tumors, 53.17% were located in the upper stomach, 25.37% in the mid, 18.54% in the distal stomach, the remaining 2.93% were found in the total stomach. The mean size was 68mm in maximum diameter, with a range of 15-150 mm. Of the one hundred and thirty-five patients, fifty appeared to be pure GSCCs, eighty-five were mixed. The median overall survival time of 195 patients was 18.50 months. The 1-, 2-, and 5-year average survival rates of 142 patients were 66.75%, 37.13%, and 20.15%, respectively. CONCLUSIONS: GSCC is a rare tumor and it is notoriously aggressive with a strong propensity for both regional and distant spread. Therapies including surgical resection, chemotherapy, and local radiotherapy, by itself or in combination with other treatment, have been used to treat GSCCs in China. To identify the most effective treatment modalities for GSCCs, we still need prospective, multicenter, randomized clinical researches.

Expression of YY1 correlates with progression and metastasis in esophageal squamous cell carcinomas.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers worldwide. Yin Yang 1 (YY1) is a ubiquitous and multifunctional zinc-finger transcription factor that plays important biological functions in cell homeostasis and tumorigenesis. The purpose of this study was to investigate the expression of YY1 in different ESCC tissues and the potential relationship with clinicopathological features. METHODS: One hundred and four ESCC tissues were collected in this study. The protein levels of YY1 were measured by immunohistochemistry. TE-1 cell invasion in vitro was assessed using the Transwell assay. RESULTS: There were no obvious differences between expression levels in patients over age 64 and those younger than 64, and no noticeable distinction was observed between males and females. However, the YY1 protein level was significantly higher in ESCC tissues with lymph node metastasis than those without lymph node metastasis (P=0.042). Furthermore, the expression of the YY1 protein was stronger in stage III-IV patients than in stage I-II patients (P=0.002), but the protein levels between different histological grades (well, moderate, or poor) showed no statistical significance. Similarly, there was no difference in YY1 expression in patients with or without lymphatic invasion. The Transwell assay revealed that the overexpression of YY1 promoted the invasion ability of TE-1 cells and the inhibition of YY1 could reverse this promotion. CONCLUSION: YY1 expression was associated with TNM stage and lymph node metastasis, suggesting that YY1 can influence human esophageal cancer progression and metastasis.

Effect of celecoxib combined with chemotherapy drug on malignant biological behaviors of gastric cancer.

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to have antitumor effects. In some tumor models, the combination of celecoxib with chemotherapy agents has shown synergistic antitumor effect; however, the effect of celecoxib combination with tegafur/gimeracil/oteracil potassium on the malignant biological behaviors of gastric cancer in nude mice is unclear. In this study, female nude mice were subcutaneously transplanted with SGC-7901 gastric cancer cells. When the tumor model formed, the mice were divided into control group, celecoxib group, tegafur/gimeracil/oteracil potassium group, and the combination of both drug regimens group. Mice were treated for 3 weeks. Following treatment, the proliferating index was calculated, apoptosis related proteins, COX-2, vascular endothelial growth factor-C (VEGF-C) and lymphatic vessel density were quantified in tumor tissues by immunohistochemistry. Apoptosis was evaluated by TUNEL staining. The results revealed that celecoxib and tegafur/gimeracil/oteracil potassium alone significantly inhibited tumor growth. The combination of these two drugs showed a synergistic antitumor effect. Both celecoxib and tegafur/gimeracil/oteracil potassium alone inhibited proliferation and promoted apoptosis. The combination of these two drugs further enhanced this anticancer effect. Both celecoxib and the combination treatment inhibited lymphangiogenesis and the expression of COX-2 and VEGF-C. However, tegafur/gimeracil/oteracil potassium treatment had no obvious effect on lymphangiogenesis. These results suggested that the combination of celecoxib and tegafur/gimeracil/oteracil potassium produced a synergistic antitumor effect, possibly by inhibiting the proliferation of tumor cells and promoting apoptosis. Celecoxib and celecoxib in combination with tegafur/gimeracil/oteracil potassium possibly by reducing the expression of COX-2, in turn down-regulating the expression of VEGF-C, resulted in the inhibition of lymphangiogenesis.