miR-143 and miR-145 inhibit stem cell characteristics of PC-3 prostate cancer cells

Huang,Shuai; Guo,Wei; Tang,Yubo; Ren,Dong; Zou,Xuenong; Peng,Xinsheng

doi:10.3892/or.2012.2015

miR-143 and miR-145 inhibit stem cell characteristics of PC-3 prostate cancer cells

Authors:
- Shuai Huang
- Wei Guo
- Yubo Tang
- Dong Ren
- Xuenong Zou
- Xinsheng Peng
View Affiliations

Affiliations: Department of Orthopaedic Surgery/Orthopaedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong Province, P.R. China
Published online on: September 4, 2012 https://doi.org/10.3892/or.2012.2015
Pages: 1831-1837

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

Emerging evidence demonstrates that cancer stem cells (CSCs) are the critical drivers of tumor progression and metastasis. The microRNAs (miRNAs) may play a crucial role in repressing/promoting metastasis of cancer by regulating CSCs. A previous study showed that miR-143 and miR-145 play an important role in regulating bone metastasis of prostate cancer (PCa), but the exact mechanism of regulation of bone metastasis of PCa is not fully understood. In this study, we found that overexpression of miR-143 and miR-145 inhibited the cell viability and colony formation of PC-3 cells from PCa bone metastasis. Furthermore, miR-143 and miR-145 suppressed tumor sphere formation and expression of CSC markers and ‘stemness’ factors including CD133, CD44, Oct4, c-Myc and Klf4 in PC-3 cells. The study further found that miR-143 and miR-145 inhibit bone invasion and tumorigenicity of PC-3 cells in vivo. Collectively, these findings demonstrate that miR-143 and miR-145 inhibit CSC properties of PC-3 cells and suggest that miR-143 and miR-145 may play a significant role in the bone metastasis progression of PCa by regulating CSC characteristics.

View Figures

View References

1	Landis SH, Murray T, Bolden S and Wingo PA: Cancer statistics, 1999. CA Cancer J Clin. 49:8–31. 1999. View Article : Google Scholar
2	Bubendorf L, Schopfer A, Wagner U, et al: Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 31:578–583. 2000. View Article : Google Scholar : PubMed/NCBI
3	Shah RB, Mehra R, Chinnaiyan AM, et al: Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program. Cancer Res. 64:9209–9216. 2004. View Article : Google Scholar : PubMed/NCBI
4	Rana A, Chisholm GD, Khan M, Sekharjit SS, Merrick MV and Elton RA: Patterns of bone metastasis and their prognostic significance in patients with carcinoma of the prostate. Br J Urol. 72:933–936. 1993. View Article : Google Scholar : PubMed/NCBI
5	Inui M, Martello G and Piccolo S: MicroRNA control of signal transduction. Nat Rev Mol Cell Biol. 11:252–263. 2010. View Article : Google Scholar
6	Schickel R, Boyerinas B, Park SM and Peter ME: MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 27:5959–5974. 2008. View Article : Google Scholar : PubMed/NCBI
7	Baranwal S and Alahari SK: miRNA control of tumor cell invasion and metastasis. Int J Cancer. 126:1283–1290. 2010.PubMed/NCBI
8	Garzon R, Calin GA and Croce CM: MicroRNAs in cancer. Annu Rev Med. 60:167–179. 2009. View Article : Google Scholar
9	Khew-Goodall Y and Goodall GJ: Myc-modulated miR-9 makes more metastases. Nat Cell Biol. 12:209–211. 2010.PubMed/NCBI
10	Nicoloso MS, Spizzo R, Shimizu M, Rossi S and Calin GA: MicroRNAs - the micro steering wheel of tumour metastases. Nat Rev Cancer. 9:293–302. 2009. View Article : Google Scholar : PubMed/NCBI
11	Li T, Li D, Sha J, Sun P and Huang Y: MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun. 383:280–285. 2009. View Article : Google Scholar : PubMed/NCBI
12	Spahn M, Kneitz S, Scholz CJ, et al: Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. Int J Cancer. 127:394–403. 2010.PubMed/NCBI
13	Kong D, Banerjee S, Ahmad A, et al: Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS One. 5:e124452010. View Article : Google Scholar : PubMed/NCBI
14	Liu C, Kelnar K, Liu B, et al: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 17:211–215. 2011. View Article : Google Scholar : PubMed/NCBI
15	Kong D, Heath E, Chen W, et al: Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One. 7:e337292012. View Article : Google Scholar : PubMed/NCBI
16	Peng X, Guo W, Liu T, et al: Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS One. 6:e203412011. View Article : Google Scholar : PubMed/NCBI
17	Su YJ, Lai HM, Chang YW, Chen GY and Lee JL: Direct reprogramming of stem cell properties in colon cancer cells by CD44. EMBO J. 30:3186–3199. 2011. View Article : Google Scholar : PubMed/NCBI
18	Clarke MF, Dick JE, Dirks PB, et al: Cancer stem cells - perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 66:9339–9344. 2006. View Article : Google Scholar
19	Sun S and Wang Z: ALDH high adenoid cystic carcinoma cells display cancer stem cell properties and are responsible for mediating metastasis. Biochem Biophys Res Commun. 396:843–848. 2010. View Article : Google Scholar : PubMed/NCBI
20	Visvader JE and Lindeman GJ: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 8:755–768. 2008. View Article : Google Scholar : PubMed/NCBI
21	Chaffer CL and Weinberg RA: A perspective on cancer cell metastasis. Science. 331:1559–1564. 2011. View Article : Google Scholar : PubMed/NCBI
22	Monteiro J and Fodde R: Cancer stemness and metastasis: therapeutic consequences and perspectives. Eur J Cancer. 46:1198–1203. 2010. View Article : Google Scholar : PubMed/NCBI
23	Hatfield S and Ruohola-Baker H: microRNA and stem cell function. Cell Tissue Res. 331:57–66. 2008. View Article : Google Scholar
24	Xu N, Papagiannakopoulos T, Pan G, Thomson JA and Kosik KS: MicroRNA-145 regulates OCT-4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell. 137:647–658. 2009. View Article : Google Scholar : PubMed/NCBI
25	Wong DJ, Segal E and Chang HY: Stemness, cancer and cancer stem cells. Cell Cycle. 7:3622–3624. 2008. View Article : Google Scholar : PubMed/NCBI
26	Zhang S, Balch C, Chan MW, et al: Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 68:4311–4320. 2008. View Article : Google Scholar : PubMed/NCBI
27	Pfeiffer MJ and Schalken JA: Stem cell characteristics in prostate cancer cell lines. Eur Urol. 57:246–254. 2010. View Article : Google Scholar : PubMed/NCBI
28	Yang M, Burton DW, Geller J, et al: The bisphosphonate olpadronate inhibits skeletal prostate cancer progression in a green fluorescent protein nude mouse model. Clin Cancer Res. 12:2602–2606. 2006. View Article : Google Scholar : PubMed/NCBI
29	Bisson I and Prowse DM: WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics. Cell Res. 19:683–697. 2009. View Article : Google Scholar : PubMed/NCBI
30	Patrawala L, Calhoun T, Schneider-Broussard R, et al: Highly purified CD44⁺ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 25:1696–1708. 2006.PubMed/NCBI
31	Trerotola M, Rathore S, Goel HL, et al: CD133, Trop-2 and alpha2beta1 integrin surface receptors as markers of putative human prostate cancer stem cells. Am J Transl Res. 2:135–144. 2010.PubMed/NCBI
32	Zöller M: CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 11:254–267. 2011.PubMed/NCBI
33	Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J and Klein B: Embryonic stem cell markers expression in cancers. Biochem Biophys Res Commun. 383:157–162. 2009. View Article : Google Scholar : PubMed/NCBI
34	Liu C and Tang DG: MicroRNA regulation of cancer stem cells. Cancer Res. 71:5950–5954. 2011. View Article : Google Scholar : PubMed/NCBI
35	Sachdeva M, Zhu S, Wu F, et al: p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Aca Sci USA. 106:3207–3212. 2009. View Article : Google Scholar : PubMed/NCBI
36	Yang YP, Chien Y, Chiou GY, Cherng JY, Wang ML, Lo WL, et al: Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials. 33:1462–1476. 2012. View Article : Google Scholar : PubMed/NCBI
37	Chiou GY, Cherng JY, Hsu HS, et al: Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial-mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma. J Control Release. 159:240–250. 2012. View Article : Google Scholar
38	Lee MY, Lu A and Gudas LJ: Transcriptional regulation of Rex1 (zfp42) in normal prostate epithelial cells and prostate cancer cells. J Cell Physiol. 224:17–27. 2010.PubMed/NCBI
39	Hayashida T, Jinno H, Kitagawa Y and Kitajima M: Cooperation of cancer stem cell properties and epithelial-mesenchymal transition in the establishment of breast cancer metastasis. J Oncol. 2011:5914272011. View Article : Google Scholar : PubMed/NCBI
40	Mani SA, Guo W, Liao MJ, et al: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 133:704–715. 2008. View Article : Google Scholar : PubMed/NCBI
41	Morel AP, Lièvre M, Thomas C, Hinkal G, Ansieau S and Puisieux A: Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One. 3:e28882008. View Article : Google Scholar : PubMed/NCBI
42	Pirozzi G, Tirino V, Camerlingo R, et al: Epithelial to mesenchymal transition by TGFβ-1 induction increases stemness characteristics in primary non small cell lung cancer cell line. PLoS One. 6:e215482011.
43	Li H, Chen X, Calhoun-Davis T, Claypool K and Tang DG: PC3 human prostate carcinoma cell holoclones contain self-renewing tumor-initiating cells. Cancer Res. 68:1820–1825. 2008. View Article : Google Scholar : PubMed/NCBI
44	Zhang K and Waxman DJ: PC3 prostate tumor-initiating cells with molecular profile FAM65B^high/MFI2^low/LEF1^low increase tumor angiogenesis. Mol Cancer. 9:3192010. View Article : Google Scholar : PubMed/NCBI
45	Morton RA, Ewing CM, Nagafuchi A, Tsukita S and Isaacs WB: Reduction of E-cadherin levels and deletion of the alpha-catenin gene in human prostate cancer cells. Cancer Res. 53:3585–3590. 1993.PubMed/NCBI