Epstein-Barr virus (EBV) is one of the major oncogenic viruses and is found in nearly 10% of gastric carcinomas. EBV is known to encode its own microRNAs (miRNAs); however, their roles have not been fully investigated. The present report is the largest series to comprehensively profile the expression of 44 known EBV miRNAs in tissue samples from patients with EBV-associated gastric carcinoma. Several miRNAs were highly expressed in EBV-associated gastric carcinoma, and in silico analysis revealed that the target genes of these EBV miRNAs had functions associated with cancer-related pathways, especially the regulation of apoptosis. Apoptosis was reduced in EBV-associated gastric carcinoma tissue samples, and gastric carcinoma cell lines infected with EBV exhibited downregulation of the proapoptotic protein Bid (the BH3-interacting domain death agonist), a member of the Bcl-2 family. The luciferase activity of the reporter vector containing the 3= untranslated region of BID was inhibited by an ebv-miR-BART4-5p mimic in gastric cancer cell lines. Transfection of an ebvmiR-BART4-5p mimic reduced Bid expression in EBV-negative cell lines, leading to reduced apoptosis under serum deprivation. The inhibition of ebv-miR-BART4-5p expression was associated with partial recovery of Bid levels in EBV-positive cell lines. The results demonstrated the antiapoptotic role of EBV miRNA via regulation of Bid expression in EBV-associated gastric carcinoma. These findings provide novel insights in the roles of EBV miRNAs in gastric carcinogenesis, which would be a potential therapeutic target. IMPORTANCEThis report is the largest series to comprehensively profile the expression of 44 known EBV miRNAs in clinical samples from EBV-associated gastric carcinoma patients. Of the EBV miRNAs, ebv-miR-BART4-5p plays an important role in gastric carcinogenesis via regulation of apoptosis. E pstein-Barr virus (EBV) is one of the major oncogenic viruses inducing various kinds of malignancies in humans. The virus originally was isolated from Burkitt's lymphoma and is associated with other hematopoietic tumors, including Hodgkin's lymphoma, extranodal nasal-type NK/T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), and lymphoproliferative disorders in immunosuppressed patients, as well as some epithelial malignancies, such as nasopharyngeal carcinoma (NPC) and gastric carcinoma (1-3). Nearly 10% of all gastric carcinomas are associated with EBV infection and form a distinct subtype of disease, exhibiting characteristic clinicopathological features (4).Several studies have investigated the roles played by EBV in carcinogenesis and have sought to show that EBV gene transcripts, including EBV nuclear antigen 2 (EBNA2) or latent membrane protein 1 (LMP1), disturb signal transduction in host cells, causing immortalization or transformation (5). Although these studies have shed light on the oncogenic properties of EBV, many unsolved problems remain.Recently, a novel class of small, noncoding RNA molecules, termed microRNAs (miRNAs), has ...

SOX9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family and is required for the development and differentiation of multiple cell lineages. To clarify the significance of SOX9 in gastric carcinoma (GC), immunohistochemical expression of SOX9 and the CpG island methylation status of SOX9 were evaluated and compared with clinicopathological factors including overall survival. SOX9 expression was immunohistochemically evaluated in 382 GC tumors and the methylation status was examined in 121 GC tumors. SOX9 expression and its methylation status in six GC cell lines, their Epstein-Barr virus (EBV)-infected cell lines, and two EBV-associated GC cell lines was also examined. The SOX9 expression increased from non-neoplastic mucosa to early cancer. High expression of SOX9 was seen in 212 cases (56%). SOX9 expression was inversely related to advanced tumor stage, vessel infiltration, nodal metastasis, and EBV infection. Fifty-eight (48%) of 121 GC tumors had a methylated promoter in GC and the methylated status was related to low expression. The expression and methylation status were not related to prognosis. Three of six cell lines had increased methylation through EBV infection and decreased SOX9 expression. Upregulation of SOX9 is related to GC development. Downregulation by promoter methylation is related to GC progression and EBV infection. SOX9 is closely related to GC carcinogenesis and EBV-associated GC carcinogenesis.

The sex of the Japanese eel could be controlled by the oral administration of DES-Na (sodium diethylstilbestrol) which also promoted growth. Elvers were reared from glass eels for more than 500 days with a commercial feed which contained DES-Na (0 , 0.5, 0.75, 1.0 ppm).All the eels were dissected at the end of the experiment to check the sex by both external appearance and histological examinations of gonads.The sex groups were divided into male, male?, female, female? and unknown by their external appearance, and into male, female, hermaphrodite, and non-sex by histological examination.The largest discrepancy (27.5%) in the two examinations was found in the male: the histological examination was found to be essential.The female ratio increased along with an increase in DES-Na.It was 7.7% in the control and 23 .2-35.4% in DES-Na groups. The male ratio was 64.1% in the control and 32.0-40.4% in DES-Na groups.The hermaphrodite ratio was 1.1-4.6%, and the non-sexual ratio was 23.8-38.0%.Females were the largest of all sex groups. The growth promoting effect was found to vary with the growth stage.

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Adiponectin is a cytokine secreted by adipocytes, whose plasma levels are decreased in obesity. Adiponectin has insulin-sensitizing, antiatherogenic, and antidiabetogenic effects. It has been shown that adiponectin may also exert antineoplastic activity through suppression of tumor proliferation and neoangiogenesis and through induction of apoptosis. Recently, low adiponectin serum concentration has been found in obesity-related malignancies, including endometrial cancer. In addition, the expression of adiponectin receptors (AdipoR1 and AdipoR2) has been documented in several human cancer tissues, but the expression has previously not been assessed in human endometrial cancer tissues. In this study, we analyzed the immunohistochemical expression of AdipoR1 and AdipoR2 in a series of surgically resected human endometrioid adenocarcinoma tissues from a total of 141 cases. Decreased AdipoR1 or AdipoR2 expression was significantly associated with histological higher grade (P=0.0026 and 0.0004, respectively). Decreased expression of AdipoR1 was associated with myometrial invasion and lymph node metastasis of endometrioid adenocarcinoma (P=0.0039 and P=0.0069, respectively). AdipoR1 and AdipoR2 immunoexpression was significantly associated with the expression of the progesterone receptor, although it was not significantly correlated with the expression of the estrogen receptor, Ki-67 or p53. Our present study raises the possibility that decreased expression of adiponectin receptors is implicated in the development, invasion, and metastasis of human endometrioid adenocarcinoma. Our findings, moreover, indicate that adiponectin receptors could be considered as therapeutic targets for endometrioid adenocarcinoma. In adiponectin receptor-positive endometrioid adenocarcinoma, we think adiponectin-based anticancer therapy is useful; however, in histological high-grade endometrioid adenocarcinoma, in which the expression levels of adiponectin receptors are relatively low, adiponectin therapy supported by adiponectin receptor induction is needed.