P2.01-014 miR-3941: A Novel microRNA That Controls IGBP1 Expression and is Associated with Malignant Progression of Lung Adenocarcinoma

S792

P2.01-014 miR-3941: A Novel microRNA That Controls IGBP1 Expression and is Associated with Malignant Progression of Lung Adenocarcinoma

Journal of Thoracic Oncology

Vol. 12 No. 1S

and miR-3941 depressed luciferase activity by targeting 3’UTR-IGBP1 in the luciferase vector (Fig1B).

Topic: Analysis of RNA Taiki Sato,1 Aya Shiba,2 Yun-Jung Kim,1 Tomoko Dai,1 Shingo Sakashita,2 Masayuki Noguchi2 1 Graduate School of Comprehensive Human Science, Department of Pathology, University of Tsukuba, Tsukuba/Japan, 2Department of Pathology, Faculty of Medicine, Univerysity of Tsukuba, Tsukuba/Japan Background: Immunoglobulin (CD79A) binding protein 1 (IGBP1) binds to PP2Ac and exerts an antiapoptotic effect. We have already reported that IGBP1 overexpression occurs during the course of malignant progression of lung adenocarcinoma (Sakashita S et al., Pathol Int. 2011). However, the molecular mechanism of IGBP1 overexpression is still unclear. A few reports have documented mutation, hypomethylation, or amplification of IGBP1, but only one study has suggested that down-regulation of miR-34b leads to high expression of IGBP1 (L-P Chen et al. Oncogene. 2011). In this study, we have detected miR-3941 as another functional microRNA that influences the expression status of IGBP1. Methods: We performed microRNA array analysis using total RNA extracted from fresh specimens of invasive lung adenocarcinoma (IGBP1+) and minimally invasive adenocarcinoma (IGBP1-). We compared the results of microRNA array with microRNAs listed in TargetScan (a microRNA database) that would potentially bind to IGBP1. Using reverse transcription-quantitative PCR (RT-qPCR), we analyzed the expression levels of candidate microRNAs in frozen specimens of lung adenocarcinoma. We also validated these microRNAs by checking IGBP1 expression and cell proliferation after they had been transfected into lung adenocarcinoma cell lines (A549, PC-9) and confirmed the direct effect of the microRNAs by luciferase reporter assay. Results: Using microRNA array and TargetScan, we selected 6 microRNAs (miR-34b, miR-138, miR-374a, miR-374b, miR-1909, miR-3941). RT-qPCR analysis showed that these microRNAs were down-regulated in invasive adenocarcinoma (IGPB1+) relative to adjacent normal lung tissue (IGBP1-) (Fig1A). We transfected these microRNAs into lung adenocarcinoma cell lines, and all of the microRNAs suppressed IGBP1 expression. Among these microRNAs, miR-34b

Conclusion: We have found that miR-3941 targets IGBP1 in addition to miR-34b. Down-regulation of both microRNAs can lead to high expression of IGBP1, and this is thought to be associated with progression of lung adenocarcinoma. Keywords: IGBP1, microRNA, Adenocarcinoma, lung

P2.01-015 Differentially Expressed microRNAs in Lung Adenocarcinoma Invert Effects of Copy Number Aberrations of Prognostic Genes Topic: Analysis of RNA Tomas Tokar,1 Emily Vucic,2 Chiara Chiara Pastrello,1 Varune Ramnarine,1 Chang-Qi Zhu,3 Kenneth Craddock,3 Frances Shepherd,4 Ming Tsao,3 Wan Lam,2 Igor Jurisica1 1Jurisica Lab, University Health Network, Toronto/ON/Canada, 2Department of Integrative Oncology, British Columbia Cancer Research Center, Vancouver/BC/Canada, 3Tsao Laboratory, University