MicroRNA-128 Downregulates Bax and Induces Apoptosis in Human Embryonic Kidney Cells

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2010 Oct 7

PMID 20924637

Citations 39

Authors

Yogita K Adlakha

Neeru Saini

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) are short ~21-nt non-coding RNA molecules that have been shown to regulate a number of biological processes. Previous reports have shown that overexpression of miR-128 in glioma cells inhibited cell proliferation. Literature also suggests that miR-128 negatively regulates prostate cancer cell invasion. Here, we show that overexpression of hsa-miR-128, a brain-enriched microRNA, induces apoptosis in HEK293T cells as elucidated by apoptosis assay, cell cycle changes, loss of mitochondrial membrane potential and multicaspase assay. By in silico analysis, we identified a putative target site within the 3' untranslated region (UTR) of Bax, a proapoptotic member of the apoptosis pathway. We found that ectopic expression of hsa-miR-128 suppressed a luciferase reporter containing the Bax-3' UTR and reduced the levels of Bax in HEK293T cells. Taken together, our study demonstrates that overexpression of hsa-miR-128 not only induces apoptosis in HEK293T cells but also is an endogenous regulator of Bax protein.

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References

Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R . Fast and effective prediction of microRNA/target duplexes. RNA. 2004; 10(10):1507-17. PMC: 1370637. DOI: 10.1261/rna.5248604. View

Godlewski J, Nowicki M, Bronisz A, Williams S, Otsuki A, Nuovo G . Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008; 68(22):9125-30. DOI: 10.1158/0008-5472.CAN-08-2629. View

Sethi P, Lukiw W . Micro-RNA abundance and stability in human brain: specific alterations in Alzheimer's disease temporal lobe neocortex. Neurosci Lett. 2009; 459(2):100-4. DOI: 10.1016/j.neulet.2009.04.052. View

Zhang Y, Chao T, Li R, Chen Y, Yan X, Gong Y . MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. J Mol Med (Berl). 2008; 87(1):43-51. DOI: 10.1007/s00109-008-0403-6. View

Su Y, Chang H, Shyue S, Hsu S . Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Biochem Pharmacol. 2005; 70(2):229-41. DOI: 10.1016/j.bcp.2005.04.026. View

Pillai R . MicroRNA function: multiple mechanisms for a tiny RNA?. RNA. 2005; 11(12):1753-61. PMC: 1370863. DOI: 10.1261/rna.2248605. View

Ott M, Norberg E, Zhivotovsky B, Orrenius S . Mitochondrial targeting of tBid/Bax: a role for the TOM complex?. Cell Death Differ. 2009; 16(8):1075-82. DOI: 10.1038/cdd.2009.61. View

Zhang L, Yu J, Park B, Kinzler K, Vogelstein B . Role of BAX in the apoptotic response to anticancer agents. Science. 2000; 290(5493):989-92. DOI: 10.1126/science.290.5493.989. View

Chen C, Li L, Lodish H, Bartel D . MicroRNAs modulate hematopoietic lineage differentiation. Science. 2003; 303(5654):83-6. DOI: 10.1126/science.1091903. View

10.

Zamore P, Haley B . Ribo-gnome: the big world of small RNAs. Science. 2005; 309(5740):1519-24. DOI: 10.1126/science.1111444. View

11.

Pfaffl M . A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001; 29(9):e45. PMC: 55695. DOI: 10.1093/nar/29.9.e45. View

12.

Lewis B, Shih I, Jones-Rhoades M, Bartel D, Burge C . Prediction of mammalian microRNA targets. Cell. 2003; 115(7):787-98. DOI: 10.1016/s0092-8674(03)01018-3. View

13.

Garzon R, Calin G, Croce C . MicroRNAs in Cancer. Annu Rev Med. 2009; 60:167-79. DOI: 10.1146/annurev.med.59.053006.104707. View

14.

Yu Z, Jian Z, Shen S, Purisima E, Wang E . Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos. Nucleic Acids Res. 2006; 35(1):152-64. PMC: 1802562. DOI: 10.1093/nar/gkl1032. View

15.

Weiss G, Bemis L, Nakajima E, Sugita M, Birks D, Robinson W . EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Ann Oncol. 2008; 19(6):1053-9. DOI: 10.1093/annonc/mdn006. View

16.

Myatt S, Wang J, Monteiro L, Christian M, Ho K, Fusi L . Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res. 2009; 70(1):367-77. PMC: 2880714. DOI: 10.1158/0008-5472.CAN-09-1891. View

17.

Radovic N, Cucic S, Altarac S . [Molecular aspects of apoptosis]. Acta Med Croatica. 2008; 62(3):249-56. View

18.

Karp X, Ambros V . Developmental biology. Encountering microRNAs in cell fate signaling. Science. 2005; 310(5752):1288-9. DOI: 10.1126/science.1121566. View

19.

Lu S, Sun Y, Shi R, Clark C, Li L, Chiang V . Novel and mechanical stress-responsive MicroRNAs in Populus trichocarpa that are absent from Arabidopsis. Plant Cell. 2005; 17(8):2186-203. PMC: 1182482. DOI: 10.1105/tpc.105.033456. View

20.

Khanna N, Jayaram H, Singh N . Benzamide riboside induced mitochondrial mediated apoptosis in human lung cancer H520 cells. Life Sci. 2004; 75(2):179-90. DOI: 10.1016/j.lfs.2003.11.026. View