RRC ID 65516
Author Sato T, Shiba-Ishii A, Kim Y, Dai T, Husni RE, Hong J, Kano J, Sakashita S, Iijima T, Noguchi M.
Title miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma.
Journal Cancer Sci
Abstract Immunoglobulin (CD79a) binding protein 1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti-apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear. In the present study, we used a microRNA (miRNA) array and TargetScan Human software to detect IGBP1-related miRNAs that regulate IGBP1 expression. The miRNA array analysis revealed more than 100 miRNAs that are dysregulated in early invasive adenocarcinoma. On the other hand, in silico analysis using TargetScan Human revealed 79 miRNAs that are associated with IGBP1 protein expression. Among the miRNAs selected by miRNA array analysis, six (miR-34b, miR-138, miR-374a, miR-374b, miR-1909, miR-3941) were also included among those selected by TargetScan analysis. Real-time reverse transcription PCR (real-time RT-PCR) showed that the six microRNAs were downregulated in invasive adenocarcinoma (IGBP1+) relative to adjacent normal lung tissue (IGBP1-). Among these microRNAs, only miR-34b and miR-3941 depressed luciferase activity by targeting 3'UTR-IGBP1 in the luciferase vector. We transfected miR-34b and miR-3941 into lung adenocarcinoma cell lines (A549, PC-9), and both of them suppressed IGBP1 expression and cell proliferation. Moreover, the transfected miR-34b and miR-3941 induced apoptosis of a lung adenocarcinoma cell line, similarly to the effect of siIGBP1 RNA. As well as miR-34b, we found that miR-3941 targeted IGBP1 specifically and was able to exclusively downregulate IGBP1 expression. These findings indicate that suppression of miR-3941 has an important role in the progression of lung adenocarcinoma at an early stage.
Volume 108(3)
Pages 536-542
Published 2017-3-1
DOI 10.1111/cas.13148
PMID 28012229
PMC PMC5378261
MeSH A549 Cells Adaptor Proteins, Signal Transducing Adenocarcinoma / genetics Adenocarcinoma / pathology* Adenocarcinoma of Lung Apoptosis / genetics* Cell Line, Tumor Cell Proliferation / genetics Disease Progression Gene Expression Regulation, Neoplastic / genetics* Humans Intracellular Signaling Peptides and Proteins / biosynthesis* Intracellular Signaling Peptides and Proteins / genetics Lung Neoplasms / genetics Lung Neoplasms / pathology* MicroRNAs / genetics* Molecular Chaperones Real-Time Polymerase Chain Reaction Transfection
IF 4.966
Resource
Human and Animal Cells A549(RCB0098) PC-9(RCB4455)