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A Migration Invasion B Migration Invasion miR-95-mimics Panc-1-control Panc-1-control miR-95-inhibitor Figure 4 Effect of miR-95 on tumor cell migration, invasion of Panc-1 cells. A: Invasion and migration assay. Representative fields of invasion (down) or migration (up) cells on the membrane (left, magnification of × 200). Average invasion or migration cell number per field (right). The invasion or migration cell number of Panc-1 transfected with miR-95-mimics drastically increased compared with that when transfected with the pairing negative control. B: The invasion or migration cell number of Panc-1 cells transfected with miR-26a-inhibitor dramatically decreased compared with that when transfected with the pairing negative control. b P < 0.01 vs Panc-1-control, n = 10. eral marker that can respond to acute manic episodes and is associated with effective mood stabilizer treatment [34] . Interestingly, recent studies indicated that miR-134 may also be involved in carcinogenesis. p53/p63/p73, the tu- WJG|www.wjgnet.com Li WG et al �� Glargine and pancreatic cancer Panc-1 cell number per field Panc-1 cell number per field 120 100 80 60 40 20 0 120 100 80 60 40 20 0 Panc-1 miR-95 mimics Panc-1-control Migration Invasion mor suppressors, were believed to be regulators of the miR-134 processing complex [35] . Our study showed that high dose glargine can significantly upregulate the expression of miR-95 (no time or dose dependent manner) and 2637 June 7, 2012|Volume 18|Issue 21| b b Migration Invasion b Panc-1 miR-95 mimics Panc-1-control b
A miR-95 B Li WG et al �� Glargine and pancreatic cancer Vector miR-95 Vector Figure 5 miR-95 promotes the growth of Sw1990 xenografts. A: miR-95 strikingly increased the growth of Sw1990 cells xenografted in nude mice; B: At the end of the experiment, all animals were sacrificed and the tumors were removed. The tumors were much heavier in miR-95 group than in the vector group. Data were shown as mean ± SD ( a P < 0.05 vs vector). miR-134 (dose dependent manner) in vitro, and for the first time investigated the role of miR-95 in pancreatic cancer. In conclusion, our study demonstrated that alterations of specific miRNAs and miRNA-related changes were important effects of glargine, suggesting an important and novel new mechanism by which glargine mediates its potent effects on cell growth and apoptosis. COMMENTS Background Glargine is widely used in the treatment of type 1 and type 2 diabetes mellitus. Recently, this insulin analogue has been suspected to be associated with an increased risk of cancer, including pancreatic cancer, but available evidence remains inconclusive. Research frontiers Anti-diabetic therapies have been shown to affect the risk of pancreatic cancer. Metformin use was associated with reduced risk, and insulin or insulin analogue use was suspected to be associated with increased risk of pancreatic cancer in diabetic patients. However, data regarding the effect of glargine, one of the long-acting insulin analogues, on pancreatic cancer are inconsistent. Several researchers WJG|www.wjgnet.com Tumor volume (mm 3 ) Weight (g) 450 400 350 300 250 200 150 100 50 0 0.6 0.5 0.4 0.3 0��2 0��1 0 miR-95 Vector 4 8 12 16 20 24 28 a a miR-95 Vector believed glargine to be a motigen, not a carcinogen. New biomarkers are needed to determine the role of glargine in the carcinogenesis of pancreatic cancer. Innovations and breakthroughs Recent reports have highlighted that miRNAs play important roles in biological processes that affect tumor progression and are promising biomarkers for cancer diagnosis or treatment. This is the first study to show the effects of high dose glargine on miRNA expression in pancreatic cancer cells. miR-95 was proved to be affected by high dose glargine and to be involoved in the carcinogenesis of pancreatic cancer. Applications By understanding the effects of glargine on pancreatic cancer cells, this study may help to clarify the role of glargine in the progress of pancreatic cancer. Terminology Glargine is a widely used insulin analog in which a 24 h action profile is achieved. MicroRNAs (miRNAs) are endogenous, non-coding small RNAs, 19-25 nucleotides in length. It has been demonstrated that miRNAs play important roles in biological processes that affect tumor progression including migration, invasion and metastasis. Peer review The authors examined the effects of high dose glargine on pancreatic cancer cells in vitro; miR-95 is up-regulated significantly by glargine. miR-95 can significantly increase pancreatic cancer cell proliferation, invasion and migration and inhibit cell apoptosis. Moreover, miR-95 is proved to inhibit pancreatic 2638 June 7, 2012|Volume 18|Issue 21| a t /d a a a
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World Journal of Gastroenterology W
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Phillip S Oates, Perth Ross C Smith
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Deepak N Amarapurkar, Mumbai Abhiji
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Trine Olsen, Tromsø Eyvind J Pauls
Page 9 and 10: Conor P Delaney, Cleveland Sharon D
Page 11 and 12: S Contents EDITORIAL FIELD OF VISIO
Page 13: Contents ACKNOWLEDGMENTS APPENDIX A
Page 19: Cereda S et al . Adjuvant treatment
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Page 46 and 47: A Macroscopir damage scores (AU) 7.
Page 48 and 49: A Total flora 12.5 B Log copy numbe
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Page 57 and 58: A Fold changes over untreated cells
Page 59: A Migration Invasion B Migration In
Page 64: Key words: Colorectal cancer; Niger
Page 67 and 68: A HT29 cells 100 C SW116 cells 40 P
Page 69 and 70: A B Ecadherin Vimentin GAPDH Zhou H
Page 71 and 72: Zhou HM et al �� Nigericin and
Page 73 and 74: Terzin V et al . Serum IgG4 in auto
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Page 96 and 97: genetic association study. BMC Canc
Page 98: ed ghrelin levels. World J Gastroen
Page 101 and 102: A Serum acylated ghrelin (pg/mL) B
Page 103 and 104: Yang YJ et al . H. pylori eradicati
Page 105 and 106: Online Submissions: http://www.wjgn
Page 107 and 108: Chen JG et al . Colorectal cancer s
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Chen JG et al . Colorectal cancer s
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Qiao CX et al . Quality of life wit
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primary liver cancer and one of the
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A A 490 Li YH et al . GABRQ in HCC
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Li YH et al . GABRQ in HCC prostate
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Online Submissions: http://www.wjgn
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Table 1 The main characteristics of
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Shen Y et al . PTEN and cetuximab e
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Shen Y et al . PTEN and cetuximab e
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Relative expression 10 8 6 4 2 0 1.
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E Methylation (%) F Methylation (%)
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Yang XX et al . Aberrant methylatio
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A B Aniwan S et al . Infliximab for
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Nishizawa T et al . Dual therapy fo
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Instructions to authors ISSN and EI
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Instructions to authors AIM (no mor
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Instructions to authors Guidelines
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