Skip to main content
Top
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression

Authors: Xinlan Fan, Xu Chen, Weixi Deng, Guangzheng Zhong, Qingqing Cai, Tianxin Lin

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells.

Methods

A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143.

Results

The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo.

Conclusions

These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. k. 2012, 62 (1): 10-29. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. k. 2012, 62 (1): 10-29.
2.
go back to reference Feldman BJ, Feldman D: The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001, 1 (1): 34-45. 10.1038/35094009.CrossRefPubMed Feldman BJ, Feldman D: The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001, 1 (1): 34-45. 10.1038/35094009.CrossRefPubMed
3.
go back to reference Visvader JE, Lindeman GJ: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008, 8 (10): 755-768. 10.1038/nrc2499.CrossRefPubMed Visvader JE, Lindeman GJ: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008, 8 (10): 755-768. 10.1038/nrc2499.CrossRefPubMed
4.
go back to reference Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ: Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005, 65 (23): 10946-10951. 10.1158/0008-5472.CAN-05-2018.CrossRefPubMed Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ: Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005, 65 (23): 10946-10951. 10.1158/0008-5472.CAN-05-2018.CrossRefPubMed
5.
go back to reference Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, et al: Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 2006, 25 (12): 1696-1708. 10.1038/sj.onc.1209327.CrossRefPubMed Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, et al: Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 2006, 25 (12): 1696-1708. 10.1038/sj.onc.1209327.CrossRefPubMed
6.
go back to reference Mimeault M, Batra SK: Characterization of nonmalignant and malignant prostatic stem/progenitor cells by Hoechst side population method. Methods Mol Biol. 2009, 568: 139-149. 10.1007/978-1-59745-280-9_8.CrossRefPubMed Mimeault M, Batra SK: Characterization of nonmalignant and malignant prostatic stem/progenitor cells by Hoechst side population method. Methods Mol Biol. 2009, 568: 139-149. 10.1007/978-1-59745-280-9_8.CrossRefPubMed
7.
go back to reference Fan X, Liu S, Su F, Pan Q, Lin T: Effective enrichment of prostate cancer stem cells from spheres in a suspension culture system. Urol Oncol. 2012, 30 (3): 314-318. 10.1016/j.urolonc.2010.03.019.CrossRefPubMed Fan X, Liu S, Su F, Pan Q, Lin T: Effective enrichment of prostate cancer stem cells from spheres in a suspension culture system. Urol Oncol. 2012, 30 (3): 314-318. 10.1016/j.urolonc.2010.03.019.CrossRefPubMed
8.
go back to reference Rybak AP, He L, Kapoor A, Cutz JC, Tang D: Characterization of sphere-propagating cells with stem-like properties from DU145 prostate cancer cells. Biochim Biophys Acta. 2011, 1813 (5): 683-694. 10.1016/j.bbamcr.2011.01.018.CrossRefPubMed Rybak AP, He L, Kapoor A, Cutz JC, Tang D: Characterization of sphere-propagating cells with stem-like properties from DU145 prostate cancer cells. Biochim Biophys Acta. 2011, 1813 (5): 683-694. 10.1016/j.bbamcr.2011.01.018.CrossRefPubMed
9.
go back to reference Lai EC: Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet. 2002, 30 (4): 363-364. 10.1038/ng865.CrossRefPubMed Lai EC: Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet. 2002, 30 (4): 363-364. 10.1038/ng865.CrossRefPubMed
10.
go back to reference Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 2006, 6 (11): 857-866. 10.1038/nrc1997.CrossRefPubMed Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 2006, 6 (11): 857-866. 10.1038/nrc1997.CrossRefPubMed
11.
go back to reference Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, et al: let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007, 131 (6): 1109-1123. 10.1016/j.cell.2007.10.054.CrossRefPubMed Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, et al: let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007, 131 (6): 1109-1123. 10.1016/j.cell.2007.10.054.CrossRefPubMed
12.
go back to reference Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, et al: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011, 17 (2): 211-215. 10.1038/nm.2284.CrossRefPubMedPubMedCentral Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, et al: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011, 17 (2): 211-215. 10.1038/nm.2284.CrossRefPubMedPubMedCentral
13.
go back to reference Hsieh IS, Chang KC, Tsai YT, Ke JY, Lu PJ, Lee KH, Yeh SD, Hong TM, Chen YL: MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway. Carcinogenesis. 2012, Epub ahead of print Hsieh IS, Chang KC, Tsai YT, Ke JY, Lu PJ, Lee KH, Yeh SD, Hong TM, Chen YL: MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway. Carcinogenesis. 2012, Epub ahead of print
14.
go back to reference Catto JW, Alcaraz A, Bjartell AS, De Vere WR, Evans CP, Fussel S, Hamdy FC, Kallioniemi O, Mengual L, Schlomm T, et al: MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol. 2011, 59 (5): 671-681. 10.1016/j.eururo.2011.01.044.CrossRefPubMed Catto JW, Alcaraz A, Bjartell AS, De Vere WR, Evans CP, Fussel S, Hamdy FC, Kallioniemi O, Mengual L, Schlomm T, et al: MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol. 2011, 59 (5): 671-681. 10.1016/j.eururo.2011.01.044.CrossRefPubMed
15.
go back to reference Spahn M, Kneitz S, Scholz CJ, Stenger N, Rudiger T, Strobel P, Riedmiller H, Kneitz B: Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. International journal of cancer Journal international du cancer. 2010, 127 (2): 394-403.PubMed Spahn M, Kneitz S, Scholz CJ, Stenger N, Rudiger T, Strobel P, Riedmiller H, Kneitz B: Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. International journal of cancer Journal international du cancer. 2010, 127 (2): 394-403.PubMed
16.
go back to reference Li T, Li D, Sha J, Sun P, Huang Y: MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun. 2009, 383 (3): 280-285. 10.1016/j.bbrc.2009.03.077.CrossRefPubMed Li T, Li D, Sha J, Sun P, Huang Y: MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun. 2009, 383 (3): 280-285. 10.1016/j.bbrc.2009.03.077.CrossRefPubMed
17.
go back to reference Xu B, Niu X, Zhang X, Tao J, Wu D, Wang Z, Li P, Zhang W, Wu H, Feng N, et al: miR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS. Mol Cell Biochem. 2011, 350 (1–2): 207-213.CrossRefPubMed Xu B, Niu X, Zhang X, Tao J, Wu D, Wang Z, Li P, Zhang W, Wu H, Feng N, et al: miR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS. Mol Cell Biochem. 2011, 350 (1–2): 207-213.CrossRefPubMed
18.
go back to reference Ru P, Steele R, Newhall P, Phillips NJ, Toth K, Ray RB: miRNA-29b suppresses prostate cancer metastasis by regulating epithelial-mesenchymal transition signaling. Mol Cancer Ther. 2012, 11 (5): 1166-1173. 10.1158/1535-7163.MCT-12-0100.CrossRefPubMed Ru P, Steele R, Newhall P, Phillips NJ, Toth K, Ray RB: miRNA-29b suppresses prostate cancer metastasis by regulating epithelial-mesenchymal transition signaling. Mol Cancer Ther. 2012, 11 (5): 1166-1173. 10.1158/1535-7163.MCT-12-0100.CrossRefPubMed
19.
go back to reference Urtreger AJ, Werbajh SE, Verrecchia F, Mauviel A, Puricelli LI, Kornblihtt AR, Bal de Kier Joffe ED: Fibronectin is distinctly downregulated in murine mammary adenocarcinoma cells with high metastatic potential. Oncol Rep. 2006, 16 (6): 1403-1410.PubMed Urtreger AJ, Werbajh SE, Verrecchia F, Mauviel A, Puricelli LI, Kornblihtt AR, Bal de Kier Joffe ED: Fibronectin is distinctly downregulated in murine mammary adenocarcinoma cells with high metastatic potential. Oncol Rep. 2006, 16 (6): 1403-1410.PubMed
20.
go back to reference Zhang X, Liu S, Hu T, He Y, Sun S: Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology. 2009, 50 (2): 490-499. 10.1002/hep.23008.CrossRefPubMed Zhang X, Liu S, Hu T, He Y, Sun S: Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology. 2009, 50 (2): 490-499. 10.1002/hep.23008.CrossRefPubMed
21.
go back to reference Fan X, Ouyang N, Teng H, Yao H: Isolation and characterization of spheroid cells from the HT29 colon cancer cell line. Int J Colorectal Dis. 2011, 26 (10): 1279-1285. 10.1007/s00384-011-1248-y.CrossRefPubMed Fan X, Ouyang N, Teng H, Yao H: Isolation and characterization of spheroid cells from the HT29 colon cancer cell line. Int J Colorectal Dis. 2011, 26 (10): 1279-1285. 10.1007/s00384-011-1248-y.CrossRefPubMed
22.
go back to reference Salvatori L, Caporuscio F, Verdina A, Starace G, Crispi S, Nicotra MR, Russo A, Calogero RA, Morgante E, Natali PG, et al: Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors. PLoS One. 2012, 7 (2): e31467-10.1371/journal.pone.0031467.CrossRefPubMedPubMedCentral Salvatori L, Caporuscio F, Verdina A, Starace G, Crispi S, Nicotra MR, Russo A, Calogero RA, Morgante E, Natali PG, et al: Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors. PLoS One. 2012, 7 (2): e31467-10.1371/journal.pone.0031467.CrossRefPubMedPubMedCentral
23.
go back to reference Yu X, Zhang X, Dhakal IB, Beggs M, Kadlubar S, Luo D: Induction of cell proliferation and survival genes by estradiol-repressed microRNAs in breast cancer cells. BMC Cancer. 2012, 12: 29-10.1186/1471-2407-12-29.CrossRefPubMedPubMedCentral Yu X, Zhang X, Dhakal IB, Beggs M, Kadlubar S, Luo D: Induction of cell proliferation and survival genes by estradiol-repressed microRNAs in breast cancer cells. BMC Cancer. 2012, 12: 29-10.1186/1471-2407-12-29.CrossRefPubMedPubMedCentral
24.
go back to reference Lin T, Dong W, Huang J, Pan Q, Fan X, Zhang C, Huang L: MicroRNA-143 as a tumor suppressor for bladder cancer. J Urol. 2009, 181 (3): 1372-1380. 10.1016/j.juro.2008.10.149.CrossRefPubMed Lin T, Dong W, Huang J, Pan Q, Fan X, Zhang C, Huang L: MicroRNA-143 as a tumor suppressor for bladder cancer. J Urol. 2009, 181 (3): 1372-1380. 10.1016/j.juro.2008.10.149.CrossRefPubMed
25.
go back to reference Szafranska AE, Davison TS, John J, Cannon T, Sipos B, Maghnouj A, Labourier E, Hahn SA: MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene. 2007, 26 (30): 4442-4452. 10.1038/sj.onc.1210228.CrossRefPubMed Szafranska AE, Davison TS, John J, Cannon T, Sipos B, Maghnouj A, Labourier E, Hahn SA: MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene. 2007, 26 (30): 4442-4452. 10.1038/sj.onc.1210228.CrossRefPubMed
26.
go back to reference Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007, 297 (17): 1901-1908. 10.1001/jama.297.17.1901.CrossRefPubMed Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007, 297 (17): 1901-1908. 10.1001/jama.297.17.1901.CrossRefPubMed
27.
go back to reference Koo S, Martin GS, Schulz KJ, Ronck M, Toussaint LG: Serial selection for invasiveness increases expression of miR-143/miR-145 in glioblastoma cell lines. BMC Cancer. 2012, 12: 143-10.1186/1471-2407-12-143.CrossRefPubMedPubMedCentral Koo S, Martin GS, Schulz KJ, Ronck M, Toussaint LG: Serial selection for invasiveness increases expression of miR-143/miR-145 in glioblastoma cell lines. BMC Cancer. 2012, 12: 143-10.1186/1471-2407-12-143.CrossRefPubMedPubMedCentral
Metadata
Title
Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression
Authors
Xinlan Fan
Xu Chen
Weixi Deng
Guangzheng Zhong
Qingqing Cai
Tianxin Lin
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-61

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine