title: The regulatory roles of miRNA and methylation on oncogene and tumor suppressor gene expression in pancreatic cancer cells.
abstract: Carcinogenesis is driven by an accumulation of mutations and genetic lesions, which leads to activation of oncogenes and inactivation of tumor suppressor genes. However, the molecular mechanisms by which the expression of these genes was regulated in pancreatic cancer remains unclear. In this study, we investigated the regulatory effects of microRNA and methylation on the expression of k-ras, TP53 and PTEN genes in pancreatic cancer cells. The protein and miRNA levels were measured by Western blotting and Northern blotting, respectively. Xenograft pancreatic tumor models were established by inoculating BxPC-1, Capan-2, and Panc-1 tumor cells into athymic nu/nu mice. A disparate level of KRAS, p53, PTEN, Dnmts, and Dicer 1 proteins as well as let-7i, miR-22, miR-143, and miR-29b miRNA was observed in BxPC-1, Capan-2, and Panc-1 cells. Knockdown of Dicer 1 expression in BxPC-3 and Panc-1 cells resulted in significant increases in KRAS, p53, PTEN, and Dnmts protein levels and significant decreases in miR-22, miR-143, let-7i, and miR-29b expression. Knockdown of Dicer 1 expression in Capan-2 cells significantly increased p53 and PTEN expression, while significantly decreased miR-22 and miR-143 expression, but had no effects on PTEN, Dnmts, let-7i, and miR-29b expression. Knockdown of Dicer 1 expression significantly inhibited xenograft BxPC-3 tumor growth, but promoted xenograft Panc-1 tumor growth. In contrast, knockdown of Dicer 1 expression had no effect on xenograft Capan-2 tumor growth. Our study suggested that different pancreatic cancer cell lines exhibited obvious discrepancies in gene expression profiles, implying that different molecular mechanisms are involved in the carcinogenesis of pancreatic cancer subclasses. Our study highlighted the importance of personalized therapy.
authors: Department of General Surgery, Central South University, Changsha 410008, PR China.
authors: Xianwei
authors: X
authors: Wang
authors: Jianfeng
authors: J
authors: Zhao
authors: Jianhua
authors: J
authors: Huang
authors: Huihuan
authors: H
authors: Tang
authors: Shuyi
authors: S
authors: Yu
authors: Yuxiang
authors: Y
authors: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics; D019175:DNA Methylation; D015257:DNA-Cytosine Methylases / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009857:Oncogenes; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D043244:Ribonuclease III / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D015257:DNA-Cytosine Methylases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053487:DEAD-box RNA Helicases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins