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miR-23b-3p and miR-130a-5p affect cell growth, migration and invasion by targeting CB1R via the Wnt/β-catenin signaling pathway in gastric carcinoma

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      Abstract

      Background

      Gastric cancer (GC) is the most common malignancy and third leading cause of cancer mortality worldwide. The identification of a sensitive biomarker as well as effective therapeutic targets for the treatment of GC is of critical importance. microRNAs play significant roles in the development of cancer and may serve as promising therapeutic targets.

      Methods

      The mRNA and protein expression of CB1R were studied both in GC cells and tissues. GC cell lines with specific gene overexpression and knockdown vectors were constructed. CCK-8 assay, matrigel invasion and colony formation assays were performed to evaluate the proliferation and invasion abilities. The binding and regulatory effects of miR-23b-3 and miR-130a-5p on CB1R mRNA were investigated using a luciferase reporter assay. Western blot analysis was performed to explore the potential interaction proteins of CB1R.

      Results

      In the present study, it was demonstrated that the cannabinoid receptor 1 (CB1R) was overexpressed, and miR-23b-3p and miR-130a-5p were downregulated, in GC cells. In addition, the results revealed that these effects are associated with malignant biological behaviors exhibited by GC cells. Furthermore, miR-23b-3p and miR-130a-5p may regulate CB1R expression via the Wnt/β-catenin signaling pathway.

      Conclusion

      Our results suggested dysregulation of CB1R expression is closely related to the malignant biological behavior of gastric cancer cells. miRNA/CB1R-based therapy may represent a promising therapeutic strategy for the clinical treatment of GC patients.

      Related collections

      Most cited references 22

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      Global cancer statistics.

      The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.
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         D Parkin,  F Bray,  J Ferlay (2005)
        Estimates of the worldwide incidence, mortality and prevalence of 26 cancers in the year 2002 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. The results are presented here in summary form, including the geographic variation between 20 large "areas" of the world. Overall, there were 10.9 million new cases, 6.7 million deaths, and 24.6 million persons alive with cancer (within three years of diagnosis). The most commonly diagnosed cancers are lung (1.35 million), breast (1.15 million), and colorectal (1 million); the most common causes of cancer death are lung cancer (1.18 million deaths), stomach cancer (700,000 deaths), and liver cancer (598,000 deaths). The most prevalent cancer in the world is breast cancer (4.4 million survivors up to 5 years following diagnosis). There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors related to lifestyle or environment, and provides a clear challenge to prevention.
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          Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.

          A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971 [controlled-trials.com].). Copyright 2006 Massachusetts Medical Society.
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            Author and article information

            Affiliations
            [1 ]Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong Province, People’s Republic of China, huangliuye_yhd@ 123456aliyun.com
            [2 ]Department of Clinical Medicine, Qingdao University Medical College, Qingdao, Shandong Province, People’s Republic of China
            Author notes
            Correspondence: Liuye Huang, Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No 20 East Road, Zhifu District, Yantai, Shandong Province, 264000, People’s Republic of China, Tel +86 0535 6691999 Ext 82703, Email huangliuye_yhd@ 123456aliyun.com
            [*]

            These authors contributed equally to this work

            Journal
            Onco Targets Ther
            Onco Targets Ther
            OncoTargets and Therapy
            OncoTargets and therapy
            Dove Medical Press
            1178-6930
            2018
            25 October 2018
            : 11
            : 7503-7512
            30498363
            6207250
            10.2147/OTT.S181706
            ott-11-7503
            © 2018 Xian et al. This work is published and licensed by Dove Medical Press Limited

            The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

            Categories
            Original Research

            Oncology & Radiotherapy

            gastric carcinoma, β-catenin, wnt, cb1r, mirna

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