title: miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc.
abstract: MicroRNAs are important gene regulators that potentially play a profound role in tumorigenesis. Increasing evidence indicates that miR-145 is a tumor suppressor capable of inhibiting breast and colon cancer cell growth both in vitro and in vivo. However, the biological function of miR-145 in non-small cell lung cancer (NSCLC) is largely unknown. In colon cancer cells, c-Myc is a confirmed direct target for miR-145. The aim of this work was to investigate the effect of miR-145 and c-Myc on proliferation of NSCLC cells, using the NSCLC cell lines A549 and H23 as models. We determined the expression level of miR-145 in tumor tissues relative to adjacent non-tumor tissues, and in NSCLC cell lines relative to non-malignant lung cells. Downregulation of miR-145 was seen in tumor tissues and the two NSCLC cell lines by real-time quantitative reverse transcription polymerase chain reaction. MTT and focus formation assays were conducted to measure cell proliferation rates. Cell growth was inhibited and the G1/S transition was blocked by miR-145 in transfection assays of A549 and H23 cells. We further showed that c-Myc was a direct target for miR-145. Introduction of miR-145 dramatically suppressed the c-Myc/eIF4E pathway, which was demonstrated to be crucial for cell proliferation in NSCLC cells. Furthermore, we found that CDK4 was regulated by miR-145 in cell cycle control. Taken together, our study results demonstrate that miR-145 inhibits proliferation of NSCLC cells through c-Myc. Increasing miR-145 expression may provide a novel approach for the treatment of NSCLC.
authors.affiliation: National Clinical Research Base of Traditional Chinese Medicine, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.forename: Huazong
authors.initials: H
authors.lastname: Zeng
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.forename: Anmei
authors.initials: A
authors.lastname: Deng
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
mesh_terms: D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C541010:MIRN145 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc