Oncotarget

Research Papers:

Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer

Joo Mi Yi, Eun-Jin Kang, Hyun-Mi Kwon, Jin-Han Bae, Keunsoo Kang, Nita Ahuja and Kwangmo Yang _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:26600-26612. https://doi.org/10.18632/oncotarget.15722

Metrics: PDF 612 views  |   HTML 841 views  |   ?  


Abstract

Joo Mi Yi1, Eun-Jin Kang1, Hyun-Mi Kwon1, Jin-Han Bae1, Keunsoo Kang2, Nita Ahuja3, Kwangmo Yang1

1Research Center, Dongnam Institute of Radiological and Medical Sciences (DIRAMS), Busan, Republic of Korea

2Department of Microbiology, Dankook University, Cheonan, Korea, Republic of Korea

3Department of Surgery, Oncology, and Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Correspondence to:

Joo Mi Yi, email: jmyi@dirams.re.kr

Kwangmo Yang, email: kmyang@dirams.re.kr

Keywords: microRNA, miR-1247, hypermethylation, tumor suppressor, pancreatic cancer

Received: October 25, 2016     Accepted: February 13, 2017     Published: February 24, 2017

ABSTRACT

Altered expression of microRNAs has been strongly implicated in human cancers, and growing evidence is emerging that a number of miRNAs are downregulated in cancer associated with CpG island hypermethylation. Although pancreatic cancer is one of the most malignant human cancers, the roles of miRNAs underlying the tumorigenesis of pancreatic cancer are still poorly understood. In the present study, we explored the molecular functional role of microRNA-1247 as tumor suppressor associated with epigenetic alteration in pancreatic cancer. CpG islands methylation of miR-1247 is frequently observed in various pancreatic cancer cell lines and in primary pancreatic tumors, but not in normal pancreatic tissue. Ectopic expression of miR-1247 in five pancreatic cancer cell lines results in suppressing of cell growth, proliferation, migration, and invasion in vitro and tumorigenicity of pancreatic cancer cells in vivo. Interestingly, we found one putative target gene of miR-1247, regulator of chromosome condensation 2 (RCC2), harbored miR-1247 target sequences in the 3′ UTR of its mRNA. In functional studies in vitro to understand the interaction between miR-1247 and RCC2, decreasing of RCC2 gene expression by miR-1247 was observed by immunoblotting and immunohistochemistry at both mRNA and protein levels. Moreover, luciferase reporter assay confirmed that RCC2 was a direct target of miR-1247. Taken together, our data suggest that CpG island hypermethylation of miR-1247 is responsible for its downregulation in pancreatic cancer, and ectopic expression of miR-1247 functions as a potential tumor suppressor targeting RCC2 in pancreatic cancer cells.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15722