MiR-29 and MiR-30 Regulate B-Myb Expression During Cellular Senescence

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Dec 29

PMID 21187425

Citations 107

Authors

Ivan Martinez

Demian Cazalla

Laura L Almstead

Joan A Steitz

Daniel DiMaio

Affiliations

Soon will be listed here.

Abstract

Cellular senescence is a form of irreversible growth arrest and a major tumor suppressor mechanism. We show here that the miR-29 and miR-30 microRNA families are up-regulated during induced and replicative senescence and that up-regulation requires activation of the Rb pathway. Expression of a reporter construct containing the 3'UTR of the B-Myb oncogene is repressed during senescence, and repression is blocked by mutations in conserved miR-29 and miR-30 binding sites in the B-Myb 3'UTR. In proliferating cells, transfection of miR-29 and miR-30 represses a reporter construct containing the wild-type but not the mutant B-Myb 3'UTR, and repression of the mutant 3'UTR is reinstituted by compensatory mutations in miR-29 and miR-30 that restore binding to the mutant sites. miR-29 and miR-30 introduction also represses expression of endogenous B-Myb and inhibits cellular DNA synthesis. Finally, interference with miR-29 and miR-30 expression inhibits senescence. These findings demonstrate that miR-29 and miR-30 regulate B-Myb expression by binding to its 3'UTR and suggest that these microRNAs play an important role in Rb-driven cellular senescence.

Citing Articles

The miR-30-5p/TIA-1 axis directs cellular senescence by regulating mitochondrial dynamics.

Tak H, Cha S, Hong Y, Jung M, Ryu S, Han S Cell Death Dis. 2024; 15(6):404.

PMID: 38858355 PMC: 11164864. DOI: 10.1038/s41419-024-06797-1.

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation.

Ibragimova M, Kussainova A, Aripova A, Bersimbaev R, Bulgakova O Cells. 2024; 13(6.

PMID: 38534394 PMC: 10969416. DOI: 10.3390/cells13060550.

The role of microRNAs in the molecular link between circadian rhythm and autism spectrum disorder.

Kim J, Kim W, Lee K Anim Cells Syst (Seoul). 2023; 27(1):38-52.

PMID: 36860270 PMC: 9970207. DOI: 10.1080/19768354.2023.2180535.

MYBL2 regulates de novo purine synthesis by transcriptionally activating IMPDH1 in hepatocellular carcinoma cells.

Zhao J, Wang W, Liu T, Zhang L, Lin D, Yao J BMC Cancer. 2022; 22(1):1290.

PMID: 36494680 PMC: 9733023. DOI: 10.1186/s12885-022-10354-4.

Improving the prediction for the response to radiotherapy of clinical tumor samples by using combinatorial model of MicroRNA expression.

Tang C, Qi J, Wu Y, Luo L, Wang Y, Wu Y Front Genet. 2022; 13:1069112.

PMID: 36482894 PMC: 9723130. DOI: 10.3389/fgene.2022.1069112.

References

Shay J, Wright W . A role for both RB and p53 in the regulation of human cellular senescence. Exp Cell Res. 1991; 196(1):33-9. DOI: 10.1016/0014-4827(91)90453-2. View

Psyrri A, DeFilippis R, Edwards A, Yates K, Manuelidis L, DiMaio D . Role of the retinoblastoma pathway in senescence triggered by repression of the human papillomavirus E7 protein in cervical carcinoma cells. Cancer Res. 2004; 64(9):3079-86. DOI: 10.1158/0008-5472.can-03-3739. View

Bates D, Li N, Liang R, Sarojini H, An J, Masternak M . MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging. Aging Cell. 2009; 9(1):1-18. PMC: 2844644. DOI: 10.1111/j.1474-9726.2009.00529.x. View

Park S, Lee J, Ha M, Nam J, Kim V . miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol. 2008; 16(1):23-9. DOI: 10.1038/nsmb.1533. View

Joaquin M, Watson R . Cell cycle regulation by the B-Myb transcription factor. Cell Mol Life Sci. 2003; 60(11):2389-401. PMC: 11138814. DOI: 10.1007/s00018-003-3037-4. View

Sala A, Casella I, Bellon T, Calabretta B, Watson R, Peschle C . B-myb promotes S phase and is a downstream target of the negative regulator p107 in human cells. J Biol Chem. 1996; 271(16):9363-7. DOI: 10.1074/jbc.271.16.9363. View

Poliseno L, Pitto L, Simili M, Mariani L, Riccardi L, Ciucci A . The proto-oncogene LRF is under post-transcriptional control of MiR-20a: implications for senescence. PLoS One. 2008; 3(7):e2542. PMC: 2435600. DOI: 10.1371/journal.pone.0002542. View

Hara E, Tsurui H, Shinozaki A, Nakada S, Oda K . Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1. Biochem Biophys Res Commun. 1991; 179(1):528-34. DOI: 10.1016/0006-291x(91)91403-y. View

Collado M, Serrano M . Senescence in tumours: evidence from mice and humans. Nat Rev Cancer. 2009; 10(1):51-7. PMC: 3672965. DOI: 10.1038/nrc2772. View

10.

Chang T, Yu D, Lee Y, Wentzel E, Arking D, West K . Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2007; 40(1):43-50. PMC: 2628762. DOI: 10.1038/ng.2007.30. View

11.

Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V . Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006; 66(24):11590-3. DOI: 10.1158/0008-5472.CAN-06-3613. View

12.

Zhang Y, Xiong Y, Yarbrough W . ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell. 1998; 92(6):725-34. DOI: 10.1016/s0092-8674(00)81401-4. View

13.

Settleman J, DiMaio D . Efficient transactivation and morphologic transformation by bovine papillomavirus genes expressed from a bovine papillomavirus/simian virus 40 recombinant virus. Proc Natl Acad Sci U S A. 1988; 85(23):9007-11. PMC: 282651. DOI: 10.1073/pnas.85.23.9007. View

14.

Campisi J . Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005; 120(4):513-22. DOI: 10.1016/j.cell.2005.02.003. View

15.

Masselink H, Vastenhouw N, Bernards R . B-myb rescues ras-induced premature senescence, which requires its transactivation domain. Cancer Lett. 2001; 171(1):87-101. DOI: 10.1016/s0304-3835(01)00631-0. View

16.

Liu N, Lucibello F, Zwicker J, Engeland K, Muller R . Cell cycle-regulated repression of B-myb transcription: cooperation of an E2F site with a contiguous corepressor element. Nucleic Acids Res. 1996; 24(15):2905-10. PMC: 146036. DOI: 10.1093/nar/24.15.2905. View

17.

Tazawa H, Tsuchiya N, Izumiya M, Nakagama H . Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A. 2007; 104(39):15472-7. PMC: 2000550. DOI: 10.1073/pnas.0707351104. View

18.

DeFilippis R, Goodwin E, Wu L, DiMaio D . Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells. J Virol. 2002; 77(2):1551-63. PMC: 140828. DOI: 10.1128/jvi.77.2.1551-1563.2003. View

19.

Lee B, Han J, Im J, Morrone A, Johung K, Goodwin E . Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell. 2006; 5(2):187-95. DOI: 10.1111/j.1474-9726.2006.00199.x. View

20.

Goodwin E, DiMaio D . Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Proc Natl Acad Sci U S A. 2000; 97(23):12513-8. PMC: 18795. DOI: 10.1073/pnas.97.23.12513. View