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摘要:
目的 探讨miRNA分子Let-7a和miR-96对胰腺癌系K-RAS基因的抑制作用及其致病机制。 方法 通过检测胰腺癌细胞系miRNA分子(Let-7a和miR-96)水平、K-RAS基因mRNA和蛋白质表达水平, 观察Let-7a和miR-96水平与K-RAS蛋白表达的关系; 并通过升高胰腺癌细胞Let-7a和miR-96水平, 检测其对K-RAS蛋白表达水平的影响。 结果 胰腺癌细胞系K-RAS的mRNA与蛋白质表达均保持在一个较高的水平; 胰腺癌细胞系miRNA分子Let-7a和miR-96水平均较低; 升高胰腺癌细胞Let-7a或miR-96水平会降低K-RAS蛋白表达水平。 结论 正常状态下, Let-7a和miR-96通过调控K-RAS基因发挥对肿瘤的抑制作用, 胰腺癌细胞的Let-7a和miR-96水平呈一定程度的降低, 削弱了对KRAS基因的抑制作用, 进而参与肿瘤的致病过程。 Abstract:Objective To explore the effects of Let-7a and miR-96 molecules on inhibition K-RAS in pancreatic cancer. Methods The levels of K-RAS mRNA and protein were detected in 9 pancreatic cancer cell lines, and the abundance of Let-7a and miR-96 in 7 of these 9 cell lines were determined to analyze the relation between the levels of Let-7a or miR-96 and K-RAS protein expression. Then, the levels of Let-7a or miR-96 was increased in PANC-1 cell line by transfection to observe K-RAS protein change. Results A high level of K-RAS mRNA was observed in 9 pancreatic cancer cell lines, and K-RAS protein was also at a higher level than normal ones. But Let-7a and miR-96 maintained were at a lower level in pancreatic cancer cell lines. An increase of Let-7a or miR-96 decreased the K-RAS protein expression in PANC-1 cell line. Conclusion Compared to normal condition, the levels of Let-7a and miR-96 decrease in pancreatic cancer, leading to the attenuation of inhibition to K-RAS, which contributes to pancreatic cancer formation and progression. -
Key words:
- pancreatic cancer /
- Let-7a /
- miR-96 /
- K-RAS
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[1] Morris JP 4th, Wang SC, Hebrok M. KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma[J]. Nat Rev Cancer, 2010, 10:683-695. doi: 10.1038/nrc2899 [2] Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family[J]. Cell, 2005, 120:635-647. doi: 10.1016/j.cell.2005.01.014 [3] Watanabe S, Ueda Y, Akaboshi S, et al. HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human pancreatic cancer cells[J]. Am J Pathol, 2009, 174:854-868. doi: 10.2353/ajpath.2009.080523 [4] Torrisani J, Bournet B, du Rieu MC, et al. let-7 MicroRNA transfer in pancreatic cancer-derived cells inhibits in vitro cell proliferation but fails to alter tumor progression[J]. Hum Gene Ther, 2009, 20:831-844. doi: 10.1089/hum.2008.134 [5] Li Y, VandenBoom TG 2nd, Kong D, et al. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells[J]. Cancer Res, 2009, 69:6704-6712. doi: 10.1158/0008-5472.CAN-09-1298 [6] Yu S, Lu Z, Liu C, et al. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer[J]. Cancer Res, 2010, 70:6015-6025. doi: 10.1158/0008-5472.CAN-09-4531 [7] Yamada Y, Enokida H, Kojima S, et al. MiR-96 and miR-183 detection in urine serve as potential tumor markers of urothelial carcinoma:correlation with stage and grade, and comparison with urinary cytology[J]. Cancer Sci, 2011, 102:522-529. doi: 10.1111/j.1349-7006.2010.01816.x [8] Weston MD, Soukup GA. MicroRNAs sound off[J]. Genome Med, 2009, 1:59. doi: 10.1186/gm59 [9] Kuhn S, Johnson SL, Furness DN, et al. miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells[J]. Proc Natl Acad Sci USA, 2011, 108:2355-2360. doi: 10.1073/pnas.1016646108 [10] Hezel AF, Kimmelman AC, Stanger BZ, et al. Genetics and biology of pancreatic ductal adenocarcinoma[J]. Genes Dev, 2006, 20:1218-1249. doi: 10.1101/gad.1415606 -
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