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Molecular Cancer
Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Research

miR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression

Authors: Fang-Ting Duan, Feng Qian, Ke Fang, Kang-Yu Lin, Wen-Tao Wang, Yue-Qin Chen

Published in: Molecular Cancer | Issue 1/2013

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Abstract

Background

MicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has been reported to be downregulated in human colorectal carcinoma (CRC) when compared to adjacent non-tumor tissue. However, its diagnostic value and role in CRC have yet to be described. CXC chemokine receptor-4 (CXCR4), which participates in multiple cell processes such as cell invasion-related signaling pathways, was predicted to be a potential target of miR-133b. The aim of this study was to investigate the associations and functions of miR-133b and CXCR4 in CRC initiation and invasion.

Methods

Mature miR-133b and CXCR4 expression levels were detected in 31 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 6 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate CXCR4 as a putative target gene of miR-133b. Regulation of CXCR4 expression by miR-133b was assessed using qRT-PCR and Western blot analysis, and the effects of exogenous miR-133b and CXCR4 on cell invasion and migration were evaluated in vitro using the SW-480 and SW-620 CRC cell lines.

Results

A significant downregulation of miR-133b was observed in 93.55% of CRC tissues, and the expression of miR-133b was much lower in metastatic tumors (stage C and D, stratified by the Modified Dukes Staging System) than in primary tumors (stage A and B). In contrast, CXCR4 protein expression significantly increased in 52.63% of CRC samples, and increased CXCR4 expression in CRC was associated with advanced tumor stage. CXCR4 was shown to be a direct target of miR-133b by luciferase reporter assays, and transfection of miR-133b mimics inhibited invasion and stimulated apoptosis of SW-480 and SW-620 CRC cells.

Conclusions

Our study demonstrated that downregulated miR-133b contributed to increased cell invasion and migration in CRC by negatively regulating CXCR4. These findings may be significant for the development of therapy target for CRC.
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Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107CrossRefPubMed
2.
Sung JJ, Lau JY, Goh KL, Leung WK: Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol. 2005, 6: 871-876. 10.1016/S1470-2045(05)70422-8CrossRefPubMed
3.
Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5CrossRefPubMed
4.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA: MicroRNA expression profiles classify human cancers. Nature. 2005, 435: 834-838. 10.1038/nature03702CrossRefPubMed
5.
Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 2006, 6: 857-866. 10.1038/nrc1997CrossRefPubMed
6.
Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006, 6: 259-269. 10.1038/nrc1840CrossRefPubMed
7.
Meltzer PS: Cancer genomics: small RNAs with big impacts. Nature. 2005, 435: 745-746. 10.1038/435745aCrossRefPubMed
8.
Fang K, Qian F, Chen YQ: MicroRNAs as regulators in normal hematopoietic and leukemia stem cells: current concepts and clinical implications. Curr Mol Med. 2012, 12: 536-546. 10.2174/156652412800620002CrossRefPubMed
9.
10.
Rao PK, Kumar RM, Farkhondeh M, Baskerville S, Lodish HF: Myogenic factors that regulate expression of muscle-specific microRNAs. Proc Natl Acad Sci USA. 2006, 103: 8721-8726. 10.1073/pnas.0602831103PubMedCentralCrossRefPubMed
11.
Boutz PL, Chawla G, Stoilov P, Black DL: MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev. 2007, 21: 71-84. 10.1101/gad.1500707PubMedCentralCrossRefPubMed
12.
Townley-Tilson WH, Callis TE, Wang D: MicroRNAs 1, 133, and 206: critical factors of skeletal and cardiac muscle development, function, and disease. Int J Biochem Cell Biol. 2010, 42: 1252-1255. 10.1016/j.biocel.2009.03.002PubMedCentralCrossRefPubMed
13.
Williams AH, Liu N, van Rooij E, Olson EN: MicroRNA control of muscle development and disease. Curr Opin Cell Biol. 2009, 21: 461-469. 10.1016/j.ceb.2009.01.029PubMedCentralCrossRefPubMed
14.
Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, Abajo A, Navarro A, Moreno I, Monzo M: Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer. 2006, 5: 29-PubMedCentralCrossRefPubMed
15.
Akcakaya P, Ekelund S, Kolosenko I, Caramuta S, Ozata DM, Xie H, Lindforss U, Olivecrona H, Lui WO: miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer. Int J Oncol. 2011, 39: 311-318.PubMed
16.
Liu L, Shao X, Gao W, Zhang Z, Liu P, Wang R, Huang P, Yin Y, Shu Y: MicroRNA-133b inhibits the growth of non-small-cell lung cancer by targeting the epidermal growth factor receptor. FEBS J. 2012, 279: 3800-3812. 10.1111/j.1742-4658.2012.08741.xCrossRefPubMed
17.
Hu G, Chen D, Li X, Yang K, Wang H, Wu W: miR-133b regulates the MET proto-oncogene and inhibits the growth of colorectal cancer cells in vitro and in vivo. Cancer Biol Ther. 2010, 10: 190-197. 10.4161/cbt.10.2.12186CrossRefPubMed
18.
Crawford M, Batte K, Yu L, Wu X, Nuovo GJ, Marsh CB, Otterson GA, Nana-Sinkam SP: MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer. Biochem Biophys Res Commun. 2009, 388: 483-489. 10.1016/j.bbrc.2009.07.143PubMedCentralCrossRefPubMed
19.
Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, Chiyomaru T, Enokida H, Nakagawa M, Matsubara H: miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int J Cancer. 2010, 127: 2804-2814. 10.1002/ijc.25284CrossRefPubMed
20.
21.
Milligan G: G protein-coupled receptor dimerization: function and ligand pharmacology. Mol Pharmacol. 2004, 66: 1-7. 10.1124/mol.104.000497.CrossRefPubMed
22.
Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier JL, Arenzana-Seisdedos F, Schwartz O, Heard JM, Clark-Lewis I, Legler DF: The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature. 1996, 382: 833-835. 10.1038/382833a0CrossRefPubMed
23.
Teicher BA, Fricker SP: CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res. 2010, 16: 2927-2931. 10.1158/1078-0432.CCR-09-2329CrossRefPubMed
24.
Kim J, Mori T, Chen SL, Amersi FF, Martinez SR, Kuo C, Turner RR, Ye X, Bilchik AJ, Morton DL: Chemokine receptor CXCR4 expression in patients with melanoma and colorectal cancer liver metastases and the association with disease outcome. Ann Surg. 2006, 244: 113-120. 10.1097/01.sla.0000217690.65909.9cPubMedCentralCrossRefPubMed
25.
Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN: Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001, 410: 50-56. 10.1038/35065016CrossRefPubMed
26.
Koshiba T, Hosotani R, Miyamoto Y, Ida J, Tsuji S, Nakajima S, Kawaguchi M, Kobayashi H, Doi R, Hori T: Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression. Clin Cancer Res. 2000, 6: 3530-3535.PubMed
27.
Schimanski CC, Schwald S, Simiantonaki N, Jayasinghe C, Gonner U, Wilsberg V, Junginger T, Berger MR, Galle PR, Moehler M: Effect of chemokine receptors CXCR4 and CCR7 on the metastatic behavior of human colorectal cancer. Clin Cancer Res. 2005, 11: 1743-1750. 10.1158/1078-0432.CCR-04-1195CrossRefPubMed
28.
Zeelenberg IS, Ruuls-Van Stalle L, Roos E: The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. Cancer Res. 2003, 63: 3833-3839.PubMed
29.
Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005, 120: 15-20. 10.1016/j.cell.2004.12.035CrossRefPubMed
30.
Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ: miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006, 34: D140-D144. 10.1093/nar/gkj112PubMedCentralCrossRefPubMed
31.
Yang JH, Li JH, Shao P, Zhou H, Chen YQ, Qu LH: starBase: a database for exploring microRNA-mRNA interaction maps from argonaute CLIP-Seq and Degradome-Seq data. Nucleic Acids Res. 2011, 39: D202-D209. 10.1093/nar/gkq1056PubMedCentralCrossRefPubMed
32.
Balkwill F: The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol. 2004, 14: 171-179. 10.1016/j.semcancer.2003.10.003CrossRefPubMed
33.
Kim J, Takeuchi H, Lam ST, Turner RR, Wang HJ, Kuo C, Foshag L, Bilchik AJ, Hoon DS: Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol. 2005, 23: 2744-2753.CrossRefPubMed
34.
Bao W, Fu HJ, Xie QS, Wang L, Zhang R, Guo ZY, Zhao J, Meng YL, Ren XL, Wang T: HER2 interacts with CD44 to up-regulate CXCR4 via epigenetic silencing of microRNA-139 in gastric cancer cells. Gastroenterology. 2011, 141: 2076-2087. e2076, 10.1053/j.gastro.2011.08.050CrossRefPubMed
35.
Leibovitz A, Stinson JC, McCombs WB, McCoy CE, Mazur KC, Mabry ND: Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 1976, 36: 4562-4569.PubMed
36.
Hong X, Chen G, Wang M, Lou C, Mao Y, Li Z, Zhang Y: STAT5a-targeting miRNA enhances chemosensitivity to cisplatin and 5-fluorouracil in human colorectal cancer cells. Mol Med Rep. 2012, 5: 1215-1219.PubMed
37.
Brand S, Dambacher J, Beigel F, Olszak T, Diebold J, Otte JM, Goke B, Eichhorst ST: CXCR4 and CXCL12 are inversely expressed in colorectal cancer cells and modulate cancer cell migration, invasion and MMP-9 activation. Exp Cell Res. 2005, 310: 117-130. 10.1016/j.yexcr.2005.07.006CrossRefPubMed
38.
Yang SX, Chen JH, Jiang XF, Wang QL, Chen ZQ, Zhao W, Feng YH, Xin R, Shi JQ, Bian XW: Activation of chemokine receptor CXCR4 in malignant glioma cells promotes the production of vascular endothelial growth factor. Biochem Biophys Res Commun. 2005, 335: 523-528. 10.1016/j.bbrc.2005.07.113CrossRefPubMed
39.
Moser B, Loetscher P: Lymphocyte traffic control by chemokines. Nat Immunol. 2001, 2: 123-128. 10.1038/84219CrossRefPubMed
40.
Ransohoff RM: Chemokines and chemokine receptors: standing at the crossroads of immunobiology and neurobiology. Immunity. 2009, 31: 711-721. 10.1016/j.immuni.2009.09.010PubMedCentralCrossRefPubMed
41.
Rossi D, Zlotnik A: The biology of chemokines and their receptors. Annu Rev Immunol. 2000, 18: 217-242. 10.1146/annurev.immunol.18.1.217CrossRefPubMed
42.
Charo IF, Ransohoff RM: The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006, 354: 610-621. 10.1056/NEJMra052723CrossRefPubMed
43.
44.
Su L, Zhang J, Xu H, Wang Y, Chu Y, Liu R, Xiong S: Differential expression of CXCR4 is associated with the metastatic potential of human non-small cell lung cancer cells. Clin Cancer Res. 2005, 11: 8273-8280. 10.1158/1078-0432.CCR-05-0537CrossRefPubMed
45.
Mori T, Doi R, Koizumi M, Toyoda E, Ito D, Kami K, Masui T, Fujimoto K, Tamamura H, Hiramatsu K: CXCR4 antagonist inhibits stromal cell-derived factor 1-induced migration and invasion of human pancreatic cancer. Mol Cancer Ther. 2004, 3: 29-37.PubMed
46.
Taichman RS, Cooper C, Keller ET, Pienta KJ, Taichman NS, McCauley LK: Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res. 2002, 62: 1832-1837.PubMed
47.
Li JK, Yu L, Shen Y, Zhou LS, Wang YC, Zhang JH: Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro. World J Gastroenterol. 2008, 14: 2308-2313. 10.3748/wjg.14.2308PubMedCentralCrossRefPubMed
48.
Chu D, Zhao Z, Zhou Y, Li Y, Li J, Zheng J, Zhao Q, Wang W: Matrix metalloproteinase-9 is associated with relapse and prognosis of patients with colorectal cancer. Ann Surg Oncol. 2012, 19: 318-325. 10.1245/s10434-011-1686-3CrossRefPubMed
49.
Tokunaga T, Oshika Y, Abe Y, Ozeki Y, Sadahiro S, Kijima H, Tsuchida T, Yamazaki H, Ueyama Y, Tamaoki N, Nakamura M: Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer. Br J Cancer. 1998, 77: 998-1002. 10.1038/bjc.1998.164PubMedCentralCrossRefPubMed
Metadata
Title
miR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression
Authors
Fang-Ting Duan
Feng Qian
Ke Fang
Kang-Yu Lin
Wen-Tao Wang
Yue-Qin Chen
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-164

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