Induction of differentiation-specific miRNAs in TPA-induced myeloid leukemia cells through MEK/ERK activation

Wang,Jing; Liu,Lijun; Xie,Lan; Xiang,Guangxin; Zhou,Yuxiang

doi:10.3892/ijmm.2012.1191

Induction of differentiation-specific miRNAs in TPA-induced myeloid leukemia cells through MEK/ERK activation

Authors:
- Jing Wang
- Lijun Liu
- Lan Xie
- Guangxin Xiang
- Yuxiang Zhou
View Affiliations

Affiliations: Medical Systems Biology Research Center, School of Medicine, Tsinghua University, Beijing 100084, P.R. China, Reproductive Medicine Center, Τhe First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, P.R. China
Published online on: November 21, 2012 https://doi.org/10.3892/ijmm.2012.1191
Pages: 59-66

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cellular microRNAs (miRNAs) are pivotal regulators involved in various biological processes through the post-transcriptional regulation of gene expression. Signaling pathways are extensively activated during 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced differentiation of human leukemia cells, but the modulation of miRNA expression and processing in this context has yet to be fully explored. In this study, we comprehensively analyzed 10 miRNAs that are consistently upregulated during TPA-induced differentiation of various leukemia cell lines by employing microarray technology. The upregulation of these miRNAs was further verified by quantitative RT-PCR, and, markedly, a subset of the miRNAs was found to be induced via the MEK/ERK signaling pathway using TPA and specific pharmacological inhibitors. Moreover, immunoblotting and quantitative RT-PCR analysis demonstrated that the expression levels of key miRNA processing machineries (i.e., Drosha, Dicer, Ago1 and Ago2) were not induced in this context, but the transcription of the miRNA products was triggered by MEK/ERK activation. Therefore, we identified the unique miRNAs that respond to TPA treatment in leukemia cells and demonstrated the essential role of the MEK/ERK signaling pathway in the induction of these miRNA transcripts.

View Figures

View References

1	Kluiver J, Kroesen BJ, Poppema S and van den Berg A: The role of microRNAs in normal hematopoiesis and hematopoietic malignancies. Leukemia. 20:1931–1936. 2006. View Article : Google Scholar : PubMed/NCBI
2	Nowak D, Stewart D and Koeffler HP: Differentiation therapy of leukemia: 3 decades of development. Blood. 113:3655–3665. 2009. View Article : Google Scholar : PubMed/NCBI
3	Schaar D, Goodell L, Aisner J, et al: A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies. Cancer Chemother Pharmacol. 57:789–795. 2006. View Article : Google Scholar : PubMed/NCBI
4	Chang SH and Hla T: Gene regulation by RNA binding proteins and microRNAs in angiogenesis. Trends Mol Med. 17:650–658. 2011. View Article : Google Scholar : PubMed/NCBI
5	Kim VN, Han J and Siomi MC: Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 10:126–139. 2009. View Article : Google Scholar : PubMed/NCBI
6	Davis-Dusenbery BN and Hata A: Mechanisms of control of microRNA biogenesis. J Biochem. 148:381–392. 2010.
7	Kasashima K, Nakamura Y and Kozu T: Altered expression profiles of microRNAs during TPA-induced differentiation of HL-60 cells. Biochem Biophys Res Commun. 322:403–410. 2004. View Article : Google Scholar : PubMed/NCBI
8	Lal A, Pan Y, Navarro F, et al: miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells. Nat Struct Mol Biol. 16:492–498. 2009. View Article : Google Scholar : PubMed/NCBI
9	Forrest AR, Kanamori-Katayama M, Tomaru Y, et al: Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation. Leukemia. 24:460–466. 2010. View Article : Google Scholar : PubMed/NCBI
10	Wang XS and Zhang JW: The microRNAs involved in human myeloid differentiation and myelogenous/myeloblastic leukemia. J Cell Mol Med. 12:1445–1455. 2008. View Article : Google Scholar : PubMed/NCBI
11	Matsumoto E, Hatanaka M, Bohgaki M and Maeda S: PKC pathway and ERK/MAPK pathway are required for induction of cyclin D1 and p21Waf1 during 12-o-tetradecanoylphorbol 13-acetate-induced differentiation of myeloleukemia cells. Kobe J Med Sci. 52:181–194. 2006.PubMed/NCBI
12	Schaar DG, Liu H, Sharma S, et al: 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dual-specificity phosphatase expression and AML cell survival. Leuk Res. 29:1171–1179. 2005. View Article : Google Scholar : PubMed/NCBI
13	Wang J, Xiang G, Mitchelson K and Zhou Y: Microarray profiling of monocytic differentiation reveals miRNA-mRNA intrinsic correlation. J Cell Biochem. 112:2443–2453. 2011. View Article : Google Scholar : PubMed/NCBI
14	Kim S, Lee HS, Lee SK, et al: 12-O-Tetradecanoyl phorbol-13-acetate (TPA)-induced growth arrest is increased by silibinin by the downregulation of cyclin B1 and cdc2 and the upregulation of p21 expression in MDA-MB231 human breast cancer cells. Phytomedicine. 17:1127–1132. 2010. View Article : Google Scholar : PubMed/NCBI
15	Park MH, Park SY and Kim Y: Induction of proline-rich tyrosine kinase2 (Pyk2) through C/EBPbeta is involved in PMA-induced monocyte differentiation. FEBS Lett. 582:415–422. 2008. View Article : Google Scholar : PubMed/NCBI
16	Guo Y, Chen Z, Zhang L, et al: Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res. 68:26–33. 2008. View Article : Google Scholar : PubMed/NCBI
17	Tusher VG, Tibshirani R and Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA. 98:5116–5121. 2001. View Article : Google Scholar : PubMed/NCBI
18	Chen C, Ridzon DA, Broomer AJ, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
19	Li X, Liu J, Zhou R, Huang S and Chen XM: Gene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation. Br J Haematol. 148:69–79. 2010. View Article : Google Scholar : PubMed/NCBI
20	Heller G, Schmidt WM, Ziegler B, et al: Genome-wide transcriptional response to 5-aza-2′-deoxycytidine and trichostatin a in multiple myeloma cells. Cancer Res. 68:44–54. 2008.
21	Cameron JE, Fewell C, Yin Q, et al: Epstein-Barr virus growth/latency III program alters cellular microRNA expression. Virology. 382:257–266. 2008. View Article : Google Scholar : PubMed/NCBI
22	Nagpal JK, Rani R, Trink B and Saini KS: Targeting miRNAs for drug discovery: a new paradigm. Curr Mol Med. 10:503–510. 2010. View Article : Google Scholar : PubMed/NCBI
23	Ichimura A, Ruike Y, Terasawa K and Tsujimoto G: miRNAs and regulation of cell signaling. FEBS J. 278:1610–1618. 2011. View Article : Google Scholar : PubMed/NCBI
24	Tsuchiya N, Izumiya M, Ogata-Kawata H, et al: Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21. Cancer Res. 71:4628–4639. 2011. View Article : Google Scholar : PubMed/NCBI
25	Huang S, He X, Ding J, et al: Upregulation of miR-23a approximately 27a approximately 24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells. Int J Cancer. 123:972–978. 2008. View Article : Google Scholar
26	Wang P, Zou F, Zhang X, et al: microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. Cancer Res. 69:8157–8165. 2009. View Article : Google Scholar : PubMed/NCBI
27	Sayed D, Rane S, Lypowy J, et al: MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell. 19:3272–3282. 2008. View Article : Google Scholar : PubMed/NCBI
28	Zaidi SK, Dowdy CR, van Wijnen AJ, et al: Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network. Cancer Res. 69:8249–8255. 2009. View Article : Google Scholar : PubMed/NCBI
29	Lin RJ, Lin YC, Chen J, et al: microRNA signature and expression of Dicer and Drosha can predict prognosis and delineate risk groups in neuroblastoma. Cancer Res. 70:7841–7850. 2010. View Article : Google Scholar : PubMed/NCBI
30	Vaksman O, Hetland TE, Trope CG, Reich R and Davidson B: Argonaute, Dicer, and Drosha are upregulated along tumor progression in serous ovarian carcinoma. Hum Pathol. May 29–2012.(Epub ahead of print).
31	Yan M, Huang HY, Wang T, et al: Dysregulated expression of dicer and drosha in breast cancer. Pathol Oncol Res. 18:343–348. 2012. View Article : Google Scholar : PubMed/NCBI
32	Frezzetti D, De Menna M, Zoppoli P, et al: Upregulation of miR-21 by Ras in vivo and its role in tumor growth. Oncogene. 30:275–286. 2011. View Article : Google Scholar : PubMed/NCBI
33	Takagi S, Nakajima M, Kida K, Yamaura Y, Fukami T and Yokoi T: MicroRNAs regulate human hepatocyte nuclear factor 4alpha, modulating the expression of metabolic enzymes and cell cycle. J Biol Chem. 285:4415–4422. 2010. View Article : Google Scholar : PubMed/NCBI
34	Schmeier S, MacPherson CR, Essack M, et al: Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation. BMC Genomics. 10:5952009. View Article : Google Scholar : PubMed/NCBI
35	Zhou R, Hu G, Gong AY and Chen XM: Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells. Nucleic Acids Res. 38:3222–3232. 2010. View Article : Google Scholar : PubMed/NCBI