MiR-16 Family Induces Cell Cycle Arrest by Regulating Multiple Cell Cycle Genes

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2008 Aug 15

PMID 18701644

Citations 233

Authors

Qin Liu

Hanjiang Fu

Fang Sun

Haoming Zhang

Yi Tie

Jie Zhu

Ruiyun Xing

Zhixian Sun

Xiaofei Zheng

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) are a class of small regulatory RNAs that are thought to be involved in diverse biological processes by regulating gene expression. Numerous miRNAs have been identified in various species, and many more miRNAs remain to be detected. Generally, hundreds of mRNAs have been predicted to be potential targets of one miRNA, so it is a great challenge to identify the genuine miRNA targets. Here, we generated the cell lines depleted of Drosha protein and screened dozens of transcripts (including Cyclin D1) regulated potentially by miRNA-mediated RNA silencing pathway. On the basis of miRNA expressing library, we established a miRNA targets reverse screening method by using luciferase reporter assay. By this method, we found that the expression of Cyclin D1 (CCND1) was regulated by miR-16 family directly, and miR-16 induced G1 arrest in A549 cells partially by CCND1. Furthermore, several other cell cycle genes were revealed to be regulated by miR-16 family, including Cyclin D3 (CCND3), Cyclin E1 (CCNE1) and CDK6. Taken together, our data suggests that miR-16 family triggers an accumulation of cells in G0/G1 by silencing multiple cell cycle genes simultaneously, rather than the individual target.

Citing Articles

The dual actions of miRNA16a in restricting Bovine Coronavirus replication through downregulation of Furin and enhancing the host immune response.

Shah A, Hemida M Sci Rep. 2024; 14(1):29308.

PMID: 39592722 PMC: 11599744. DOI: 10.1038/s41598-024-80708-4.

An ALS-associated mutation dysregulates microglia-derived extracellular microRNAs in a sex-specific manner.

Christoforidou E, Moody L, Joilin G, Simoes F, Gordon D, Talbot K Dis Model Mech. 2024; 17(5).

PMID: 38721655 PMC: 11152562. DOI: 10.1242/dmm.050638.

The lncRNA inhibits miR-15/16 to enhance cytotoxic T cell activation and memory cell formation.

Wheeler B, Gagnon J, Zhu W, Munoz-Sandoval P, Wong S, Simeonov D Elife. 2023; 12.

PMID: 38127070 PMC: 10735224. DOI: 10.7554/eLife.87900.

The Role and Antagonistic Effects of miR-16-5p in the Regulation of ADP-Ribosylation Factor-Like Tumor Suppressor Gene 1 in Lung Cancer Cells.

Yuksel T, Bozgeyik E, Bozgeyik I Eurasian J Med. 2023; 55(3):204-207.

PMID: 37909191 PMC: 10724712. DOI: 10.5152/eurasianjmed.2023.23073.

In Vitro microRNA Expression Profile Alterations under CDK4/6 Therapy in Breast Cancer.

Asberger J, Berner K, Bicker A, Metz M, Jager M, Weiss D Biomedicines. 2023; 11(10).

PMID: 37893081 PMC: 10604872. DOI: 10.3390/biomedicines11102705.

References

Ortega S, Malumbres M, Barbacid M . Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta. 2002; 1602(1):73-87. DOI: 10.1016/s0304-419x(02)00037-9. View

Carleton M, Cleary M, Linsley P . MicroRNAs and cell cycle regulation. Cell Cycle. 2007; 6(17):2127-32. DOI: 10.4161/cc.6.17.4641. View

Linsley P, Schelter J, Burchard J, Kibukawa M, Martin M, Bartz S . Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol. 2007; 27(6):2240-52. PMC: 1820501. DOI: 10.1128/MCB.02005-06. View

Olsen P, Ambros V . The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol. 2000; 216(2):671-80. DOI: 10.1006/dbio.1999.9523. View

Alao J . The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Mol Cancer. 2007; 6:24. PMC: 1851974. DOI: 10.1186/1476-4598-6-24. View

Gregory R, Chendrimada T, Cooch N, Shiekhattar R . Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005; 123(4):631-40. DOI: 10.1016/j.cell.2005.10.022. View

Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli M, Degli Uberti E . miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol. 2005; 204(1):280-5. DOI: 10.1002/jcp.20282. View

Lewis B, Burge C, Bartel D . Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005; 120(1):15-20. DOI: 10.1016/j.cell.2004.12.035. View

Gregory R, Yan K, Amuthan G, Chendrimada T, Doratotaj B, Cooch N . The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004; 432(7014):235-40. DOI: 10.1038/nature03120. View

10.

Slack F, Basson M, Liu Z, Ambros V, Horvitz H, Ruvkun G . The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell. 2000; 5(4):659-69. DOI: 10.1016/s1097-2765(00)80245-2. View

11.

Krutzfeldt J, Poy M, Stoffel M . Strategies to determine the biological function of microRNAs. Nat Genet. 2006; 38 Suppl:S14-9. DOI: 10.1038/ng1799. View

12.

Huang J, Liang Z, Yang B, Tian H, Ma J, Zhang H . Derepression of microRNA-mediated protein translation inhibition by apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members. J Biol Chem. 2007; 282(46):33632-33640. DOI: 10.1074/jbc.M705116200. View

13.

He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S . The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2005; 102(52):19075-80. PMC: 1323209. DOI: 10.1073/pnas.0509603102. View

14.

Cimmino A, Calin G, Fabbri M, Iorio M, Ferracin M, Shimizu M . miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005; 102(39):13944-9. PMC: 1236577. DOI: 10.1073/pnas.0506654102. View

15.

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

16.

le Sage C, Nagel R, Egan D, Schrier M, Mesman E, Mangiola A . Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 2007; 26(15):3699-708. PMC: 1949005. DOI: 10.1038/sj.emboj.7601790. View

17.

Lee Y, Jeon K, Lee J, Kim S, Kim V . MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002; 21(17):4663-70. PMC: 126204. DOI: 10.1093/emboj/cdf476. View

18.

Denli A, Tops B, Plasterk R, Ketting R, Hannon G . Processing of primary microRNAs by the Microprocessor complex. Nature. 2004; 432(7014):231-5. DOI: 10.1038/nature03049. View

19.

Stacey D . Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells. Curr Opin Cell Biol. 2003; 15(2):158-63. DOI: 10.1016/s0955-0674(03)00008-5. View

20.

Sun F, Fu H, Liu Q, Tie Y, Zhu J, Xing R . Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett. 2008; 582(10):1564-8. DOI: 10.1016/j.febslet.2008.03.057. View