MicroRNA-148b and microRNA-152 reactivate tumor suppressor genes through suppression of DNA methyltransferase-1 gene in pancreatic cancer cell lines

作者: Masoumeh Azizi , Ladan Teimoori-Toolabi , Mohsen Karimi Arzanani , Kayhan Azadmanesh , Pezhman Fard-Esfahani

DOI: 10.4161/CBT.27630

关键词:

摘要: Overexpression of DNA methyltransferase 1 (DNMT-1) is observed mostly in pancreatic cancer and it can cause tumor suppressor genes silencing this disease. Recent studies suggest that abnormal expressions microRNAs (miRs) are involved pathogenesis different types human cancers including cancer. In study we aimed to investigate the effect miR-148b -152 on reverting tumorigenic phenotype cell lines. In order whether regulation DNMT-1, luciferase reporter assay was used confirmed DNMT-1 mRNA could be a target for miR-152. Furthermore, overexpression lines (MIA PaCa-2 AsPC-1) decreased expression (53% 59% respectively), returned methylation normal patterns induced re-expression genes, like BNIP3 (4.7- 3.8-fold) SPARC (5.3- 2.9-fold) respectively. Moreover, introduced inhibit proliferation MIA (35% 37% respectively) AsPC-1 (39% 40% The apoptosis rates PaCa-1 after treatment with were 10% 8% respectively; while these 16% 11% Conclusively findings mean miRs targeting modifying status such as applied killing cells decreasing tumorigenicity cells.

参考文章(48)
Angelo M. De Marzo, Valerie L. Marchi, Xiaohui Lin, William G. Nelson, Eddy S. Yang, Ravi Veeraswamy, Abnormal Regulation of DNA Methyltransferase Expression during Colorectal Carcinogenesis Cancer Research. ,vol. 59, pp. 3855- 3860 ,(1999)
Ralph H. Hruban, Minoru Toyota, Charles J. Yeo, Jean-Pierre J. Issa, Kimberly M. Walter, Michael Goggins, Hal Skinner, Takashi Ueki, Identification and characterization of differentially methylated CpG islands in pancreatic carcinoma. Cancer Research. ,vol. 61, pp. 8540- 8546 ,(2001)
Noriyuki Omura, Michael Goggins, Epigenetics and Epigenetic Alterations in Pancreatic Cancer International Journal of Clinical and Experimental Pathology. ,vol. 2, pp. 310- 326 ,(2009)
Tsuyoshi Etoh, Yae Kanai, Saori Ushijima, Tohru Nakagawa, Yukihiro Nakanishi, Mitsuru Sasako, Seigo Kitano, Setsuo Hirohashi, Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. American Journal of Pathology. ,vol. 164, pp. 689- 699 ,(2004) , 10.1016/S0002-9440(10)63156-2
Norihiro Sato, Noriyoshi Fukushima, Naoki Maehara, Hiroyuki Matsubayashi, Jens Koopmann, Gloria H Su, Ralph H Hruban, Michael Goggins, SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor–stromal interactions Oncogene. ,vol. 22, pp. 5021- 5030 ,(2003) , 10.1038/SJ.ONC.1206807
Norihiro Sato, Antony R Parker, Noriyoshi Fukushima, Yohei Miyagi, Christine A Iacobuzio-Donahue, James R Eshleman, Michael Goggins, Epigenetic inactivation of TFPI-2 as a common mechanism associated with growth and invasion of pancreatic ductal adenocarcinoma Oncogene. ,vol. 24, pp. 850- 858 ,(2005) , 10.1038/SJ.ONC.1208050
Ang Li, Noriyuki Omura, Seung-Mo Hong, Michael Goggins, Pancreatic cancer DNMT1 expression and sensitivity to DNMT1 inhibitors Cancer Biology & Therapy. ,vol. 9, pp. 321- 329 ,(2010) , 10.4161/CBT.9.4.10750
Dun-Fa Peng, Yae Kanai, Morio Sawada, Saori Ushijima, Nobuyoshi Hiraoka, Tomoo Kosuge, Setsuo Hirohashi, Increased DNA methyltransferase 1 (DNMT1) protein expression in precancerous conditions and ductal carcinomas of the pancreas Cancer Science. ,vol. 96, pp. 403- 408 ,(2005) , 10.1111/J.1349-7006.2005.00071.X
Jing Li, M. Guillaume Wientjes, Jessie L.-S. Au, Pancreatic cancer: pathobiology, treatment options, and drug delivery Aaps Journal. ,vol. 12, pp. 223- 232 ,(2010) , 10.1208/S12248-010-9181-5