MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting CCND1.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3'-untranslated region (3'UTR). In this study, we found that miR-490-3p is significantly down-regulated in A549 lung cancer cells compared with the normal bronchial epithelial cell line. To better characterize the role of miR-490-3p in A549 cells, we performed a gain-of-function analysis by transfecting the A549 cells with chemically synthesized miR-490-3P mimics. Overexpression of miR-490-3P evidently inhibits cell proliferation via G1-phase arrest. We also found that forced expression of miR-490-3P decreased both mRNA and protein levels of CCND1, which plays a key role in G1/S phase transition. In addition, the dual-luciferase reporter assays indicated that miR-490-3P directly targets CCND1 through binding its 3'UTR. These findings indicated miR-490-3P could be a potential suppressor of cellular proliferation.

[1]  J. Alao,et al.  Molecular Cancer BioMed Central Review The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention , 2007 .

[2]  Yi Tie,et al.  Downregulation of CCND1 and CDK6 by miR‐34a induces cell cycle arrest , 2008, FEBS letters.

[3]  M. Malumbres,et al.  MicroRNAs and the cell cycle. , 2011, Biochimica et biophysica acta.

[4]  J. Xu,et al.  WT1 Promotes Cell Proliferation in Non-Small Cell Lung Cancer Cell Lines through Up-Regulating Cyclin D1 and p-pRb In Vitro and In Vivo , 2013, PloS one.

[5]  E. Sotillo,et al.  Shielding the messenger (RNA): microRNA-based anticancer therapies. , 2011, Pharmacology & therapeutics.

[6]  George Coukos,et al.  Mechanisms of microRNA deregulation in human cancer , 2008, Cell cycle.

[7]  E. Wang,et al.  Interleukin-7 up-regulates cyclin D1 via activator protein-1 to promote proliferation of cell in lung cancer , 2011, Cancer Immunology, Immunotherapy.

[8]  K. Stoeber,et al.  The cell cycle and cancer , 2012, The Journal of pathology.

[9]  M. Barbacid,et al.  Cell cycle, CDKs and cancer: a changing paradigm , 2009, Nature Reviews Cancer.

[10]  Zhe Wang,et al.  MiR-490-3p modulates the proliferation of vascular smooth muscle cells induced by ox-LDL through targeting PAPP-A. , 2013, Cardiovascular research.

[11]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[12]  Thomas Tuschl,et al.  miRNAs in human cancer , 2011, The Journal of pathology.

[13]  Xiangyi Zheng,et al.  MicroRNA-449a acts as a tumor suppressor in human bladder cancer through the regulation of pocket proteins. , 2012, Cancer letters.

[14]  Richard J Jackson,et al.  How Do MicroRNAs Regulate Gene Expression? , 2007, Science's STKE.

[15]  Yufei Huang,et al.  De-Regulated MicroRNAs in Pediatric Cancer Stem Cells Target Pathways Involved in Cell Proliferation, Cell Cycle and Development , 2013, PloS one.

[16]  E. Dmitrovsky,et al.  UBE1L causes lung cancer growth suppression by targeting cyclin D1 , 2008, Molecular Cancer Therapeutics.

[17]  Min Liu,et al.  miR-490-3p Modulates Cell Growth and Epithelial to Mesenchymal Transition of Hepatocellular Carcinoma Cells by Targeting Endoplasmic Reticulum-Golgi Intermediate Compartment Protein 3 (ERGIC3)* , 2012, The Journal of Biological Chemistry.

[18]  Kaishun Hu,et al.  MiR-138 suppressed nasopharyngeal carcinoma growth and tumorigenesis by targeting the CCND1 oncogene , 2012, Cell cycle.

[19]  K. Kelnar,et al.  Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. , 2010, Cancer research.

[20]  Xiaolong Yang,et al.  MicroRNA-193b represses cell proliferation and regulates cyclin D1 in melanoma. , 2010, The American journal of pathology.

[21]  P. Kaldis,et al.  Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms , 2009, Oncogene.

[22]  P. Hinds,et al.  Cyclins and cdks in development and cancer: a perspective , 2005, Oncogene.

[23]  J. Massagué,et al.  G1 cell-cycle control and cancer , 2004, Nature.

[24]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[25]  M. Imoto,et al.  Functions of cyclin D1 as an oncogene and regulation of cyclin D1 expression , 2007, Cancer science.

[26]  J. Diehl,et al.  Nuclear cyclin D1: An oncogenic driver in human cancer , 2009, Journal of cellular physiology.

[27]  Salvatore Campo,et al.  Circulating microRNAs: new biomarkers in diagnosis, prognosis and treatment of cancer (review). , 2012, International journal of oncology.

[28]  Y. Huo,et al.  MicroRNA‐503 suppresses proliferation and cell‐cycle progression of endometrioid endometrial cancer by negatively regulating cyclin D1 , 2013, The FEBS journal.

[29]  C. Croce.  Causes and consequences of microRNA dysregulation in cancer , 2009, Nature Reviews Genetics.

[30]  H. Kung,et al.  MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. , 2009, Biochemical and biophysical research communications.

[31]  Chenguang Wang,et al.  Minireview: Cyclin D1: normal and abnormal functions. , 2004, Endocrinology.

[32]  E. H. Mercer,et al.  Fibrous insulin (F-insulin). , 1953, Biochimica et biophysica acta.

[33]  N. Perkins,et al.  Regulation of cyclin D1 gene expression. , 2010, Biochemical Society transactions.