ABSTRACT
Recent studies have implied that circHIPK3, an abundant circular RNA (circRNA), participates in tumorigenesis and cancer progression. Its expression and potential functions in human gallbladder cancer were examined in this study. We show that circHIPK3 is upregulated in human gallbladder cancer cells. But its level is low in gallbladder epithelial cells. circHIPK3 silencing by targeted siRNA potently inhibited survival and proliferation of established and primary human gallbladder cancer cells, while inducing cell apoptosis. Conversely, ectopic over-expression of circHIPK3 can further promote cancer cell proliferation. In gallbladder cancer cells, circHIPK3 sponged the tumor-suppressive microRNA-124 (miR-124) to sequester and inhibit its activity, thereby leading to increased expression of miR-124 targets, including ROCK1 (rho-associated protein kinase 1) and CDK6 (rho-associated protein kinase). Ectopic over-expression of miR-124â¯bâ¯y a lentiviral vector mimicked and abolished actions by circHIPK3 siRNA in gallbladder cancer cells. At last, we show that circHIPK3 is upregulated in human gallbladder cancer tissues, which is correlated with miR-124 downregulation and ROCK1-CDK6 upregulation. Together, we conclude that circHIPK3 promotes gallbladder cancer cell growth possibly by sponging miR-124. The over-expressed circHIPK3 could be a novel therapeutic target and diagnosis marker of human gallbladder cancer.
Subject(s)
Cell Proliferation/genetics , Gallbladder Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , RNA, Neoplasm/genetics , RNA/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Survival/genetics , Gallbladder Neoplasms/pathology , Humans , RNA Interference , RNA, Circular , rho-Associated Kinases/geneticsABSTRACT
Objective To investigate effective treatment modalities and the related factors influencing prognosis of patients with gallbladder cancer.Methods The clinical data of 76 gallbladder carcinoma patients admitted to the Department of General Surgery,PLA Nanjing General Hospital from January 2005 to October 2015 were analyzed retrospectively.Follow-up was carried out via telephone or outpatient service until January 2016.Cox regression and Kaplan-Meier models were performed for survival analysis.Results 69 patients were treated with surgery and/or postoperative adjuvant chemotherapy.The remaining 7 patients with liver or distant metastases who did not undergo surgery received chemotherapy.24 patients died from cancer relapse,37 patients died from disease progression after giving up treatment,and 7 patients were lost to follow-up.The remaining 8 patients were still alive at the time of follow-up.The depth of cancer invasion (HR =2.736),the type surgical procedure (HR =2.207),and adjuvant chemotherapy (HR =0.603) were significant impact factors of survival for GBC patients.Adjuvant chemotherapy was a protective factor.The average survival in the chemotherapy-naive group was (10.6 ± 1.9) months,the single chemotherapy group (18.5 ± 2.8) months,and the combined chemotherapy group (26.9 ± 6.4) months.There were no significant differences among these groups.Conclusions The depth of cancer invasion,types of surgical procedure particularly radical cholecystectomy,and adjuvant chemotherapy were significant factors of survival in patients with GBC.Radical cholecystectomy combined with arterial and intravenous chemotherapy using gemcitabine and oxaliplatin showed benefits in survival in GBC patients.
ABSTRACT
Sepsis caused by complicated intra-abdominal infection has a poor prognosis since the mechanism of sepsis has not been fully clarified .Research about the effect of Receptor of Advanced Glycation Endproducts on sepsis was paid extensive attention . In this paper , the construction and function of RAGE , the relationship between RAGE and inflammation and action of RAGE during sepsis are summarized .
