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STUDY DESIGN: To investigate the specific mechanisms by which Golgi phosphoprotein 3 (GOLPH3) affects the progression of gastric cancer and to explore its clinical significance. METHODS: Immunohistochemical analysis was used to evaluate the correlations between GOLPH3, phosphorylated mTOR (p-mTOR), phosphorylated Akt (p-Akt), phosphorylated p70S6 (p-p70S6), phosphorylated 4E-BP1 (p-4E-BP1) and the clinicopathological features of gastric cancer. The mRNA expression levels of GOLPH3, mTOR, Akt, p70S6 and 4E-BP1 in gastric cancer, carcinoma-adjacent and paired normal tissue were analyzed using RT-PCR. Western blotting was used to determine the protein expression of GOLPH3, p-mTOR, p-Akt, p-p70S6 and p-4E-BP1 in tissues. RESULTS: High expression protein levels of GOLPH3, p-AKT, p-mTOR, p70S6, p-4E-BP1 were positively associated with histological grade (p

Background Gastrointestinal neuroendocrine neoplasms (GI-NENs) are often located in the deep mucosa or submucosa, and the efficacy of endoscopic biopsy for diagnosis and treatment of GI-NENs is not fully understood. Objective The current study analyzed GI-NENs, especially those diagnosed pathologically and resected endoscopically, and focused on the biopsy and cold biopsy forceps polypectomy (CBP) to analyze their roles in diagnosing and treating GI-NENs. Methods Clinical data of all GI-NENs were reviewed from January 2006 to March 2012. Histopathology was used to diagnose GI-NENs, which were confirmed by immunohistochemistry. Results 67.96% GI-NENs were diagnosed pathologically by endoscopy. Only 26.21% were diagnosed pathologically by biopsies before treatment. The diagnostic rate was significantly higher in polypoid (76.47%) and submucosal lesions (68.75%), than in ulcerative lesions (12.00%). However, biopsies were only taken in 56.31% patients, including 51.52% of polypoid lesions, 35.56% of submucosal lesions and 100.00% of ulcerative lesions. Endoscopic resection removed 61.76% of GI-NENs, including six by CBP, 14 by snare polypectomy with electrocauterization, 28 by endoscopic mucosal resection (EMR) and 15 by endoscopic submucosal dissection (ESD). 51.52% polypoid GI-NENs had infiltrated the submucosa under microscopic examination. CBP had a significantly higher rate of remnant (33.33%) than snare polypectomy with electrocauterization, EMR and ESD (all 0.00%). Conclusions Biopsies for all polypoid and submucosal lesions will improve pre-operative diagnosis. The high rate of submucosal infiltration of polypoid GI-NENs determined that CBP was inadequate in the treatment of GI-NENs. Diminutive polypoid GI-NENs that disappeared after CBP had a high risk of remnant and should be closely followed up over the long term.

Increasing evidence shows that dysregulation of microRNAs (miRNAs) is involved in malignant transformation. We investigated the clinical significance of miR-650 and its involvement in chemoresistance to docetaxel. Our results showed that the relative expression level of miR-650 was significantly higher in LAD tissues than in corresponding nontumor tissues and high level of miR-650 expression was found to be significantly associated with high incidence of lymph node metastasis, advanced clinical stage and poor prognosis of LAD patients. Univariate and multivariate analyses indicated that high miR-650 expression was an independent prognostic factor for survival. Also, we found that the level of miR-650 in LAD tissues was correlated with the response of patients to docetaxel-based chemotherapy. Silencing of miR-650 could increase the in vitro sensitivity of docetaxel-resistant LAD cells to docetaxel, while upregulation of miR-650 decreased the sensitivity of parental LAD cells to docetaxel both in vitro and in vivo. Additionally, silencing of miR-650 could enhance the caspase-3-dependent apoptosis, which might be correlated with the decreased ratio of Bcl-2/Bax. Further researches suggested that inhibitor of growth 4 (ING4) was a direct target of miR-650. Downregulated or upregulated ING4 expression could partially rescue the effects of miR-650 inhibitor or mimics in docetaxel-resistant or parental LAD cells. Furthermore, we found that ING4 was upregulated in docetaxel-responding LAD tissues, and its expression was inversely correlated with miR-650. Thus, miR-650 is a novel prognostic marker in LAD and its expression is a potential indicator of chemosensitivity to docetaxel-based chemotherapy regimen.

As a newly identified and characterized gene, p42.3 is associated with cell proliferation and tumorigenicity. The expression of p42.3 is upregulated in human gastric cancer (GC), but its underlying mechanisms of action are not well understood. MicroRNAs (miRNAs) are known to play vital regulatory roles in many cellular processes. Here we utilized bioinformatics and experimental approaches to investigate the regulatory relationship between miRNAs and the p42.3 gene. We showed that miR-29a could repress p42.3 expression at both the mRNA and protein levels via directly binding to its 3’UTR. Furthermore, an inverse relationship was observed between miR-29a and p42.3 expression in gastric cancer cell lines and GC tissue samples, especially in cases where p42.3 was downregulated. Taken together, we have elucidated previously unrecognized roles of miR-29a and indicated that miR-29a may function, at least partially, by targeting the p42.3 gene in human GC.

We induced mutants, stripe1-2 (st1-2) and stripe1-3 (st1-3), from rice (Oryza sativa L.) Indica 9311 using Ethyl methanesulfonate (EMS). Both st1-2 and st1-3 mutants encoded the small subunit of ribonucleotide reductase 1 (RNRS1), differed in the location of the mutated base, and displayed white-stripe from the L2 stage through maturity. The mutants were sensitive to temperature, and their chlorophyll content increased with the increase in temperature; however, they did not revert to normal green leaf phenotype under field conditions. The mutant st1-2 showed loosely arranged thylakoid lamellar structure as compared with wild-type (WT) plants. Contrastingly, st1-3 displayed normal thylakoid lamellar structure, good agronomic traits, and higher yield than st1-2 but lower yield than WT. Three-dimensional structure prediction for RNRS1 indicated that the mutation in Val-171 residue in st1-2 influenced the connection of RNRS1 to iron, causing abnormal development of chloroplasts. Real-time PCR analysis showed that the expression levels associated with chlorophyll biosynthetic pathway and photosynthesis were affected in st1-2 and st1-3 at different temperatures and different developmental stages.