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Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

MicroRNA-30a regulates cell proliferation and tumor growth of colorectal cancer by targeting CD73

Authors: Minghao Xie, Huabo Qin, Qianxin Luo, Qunsheng Huang, Xiaosheng He, Zihuan Yang, Ping Lan, Lei Lian

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

MicroRNAs are non-coding RNAs which regulate a variety of cellular functions in the development of tumors. Among the numerous microRNAs, microRNA-30a (miR-30a) is thought to play an important role in the processes of various human tumors. In this study, we aimed to explore the role of miR-30a in the process of colorectal cancer (CRC).

Methods

The quantitative real-time PCR and western blot analysis were used to detect the expressions of miR-30a and CD73 in CRC cell lines and clinical tissues. The luciferase reporter assay was conducted to validate the association between miR-30a and CD73. The CCK-8, terminal deoxynucleotidyl transferase dUTP -biotin nick end labeling (TUNEL) assays and cell cycle flow cytometry were carried out to verify the biological functions of miR-30a in vitro. The nude mouse tumorigenicity experiment was used to clarify the biological role of miR-30a in vivo.

Results

The expression of miR-30a was significantly reduced in tumor cells and tissues of CRC. The proliferation ability of CRC cells was suppressed and the apoptosis of cells was promoted when miR-30a is over-regulated, however, the biological effects would be inverse since the miR-30a is down-regulated. CD73 is thought to be a target binding gene of miR-30a because miR-30a can bind directly to the 3′-UTR of CD73 mRNA, subsequently reducing its expression. The proliferation suppression of the CRC cells mediated by miR-30a could be rescued after up-regulating the expression of CD73.

Conclusions

MiR-30a plays an important role on regulating the cell proliferation and apoptosis, thus affecting the growth of the tumor in CRC. And it may participate in the disease process of CRC by regulating the expression of CD73.
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Literature
2.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed
4.
go back to reference Monroig-Bosque PC, Rivera CA, Calin GA. MicroRNAs in cancer therapeutics: "from the bench to the bedside". Expert Opin Biol Ther. 2015;15:1381–5.CrossRefPubMedCentral Monroig-Bosque PC, Rivera CA, Calin GA. MicroRNAs in cancer therapeutics: "from the bench to the bedside". Expert Opin Biol Ther. 2015;15:1381–5.CrossRefPubMedCentral
5.
6.
go back to reference Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMed Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMed
7.
go back to reference He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.CrossRefPubMedPubMedCentral He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.CrossRefPubMedPubMedCentral
9.
go back to reference Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.CrossRefPubMedPubMedCentral Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.CrossRefPubMedPubMedCentral
10.
go back to reference Boufraqech M, Nilubol N, Zhang L, Gara SK, Sadowski SM, Mehta A, He M, Davis S, Dreiling J, Copland JA, Smallridge RC, Quezado MM, Kebebew E. miR30a inhibits LOX expression and anaplastic thyroid cancer progression. Cancer Res. 2015;75:367–77.CrossRefPubMed Boufraqech M, Nilubol N, Zhang L, Gara SK, Sadowski SM, Mehta A, He M, Davis S, Dreiling J, Copland JA, Smallridge RC, Quezado MM, Kebebew E. miR30a inhibits LOX expression and anaplastic thyroid cancer progression. Cancer Res. 2015;75:367–77.CrossRefPubMed
11.
go back to reference Zhang J, Shen C, Wang L, Ma Q, Xia P, Qi M, Yang M, Han B. Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4. Biochem Biophys Res Commun. 2014;452:746–52.CrossRefPubMed Zhang J, Shen C, Wang L, Ma Q, Xia P, Qi M, Yang M, Han B. Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4. Biochem Biophys Res Commun. 2014;452:746–52.CrossRefPubMed
12.
go back to reference Zhang Q, Tang Q, Qin D, Yu L, Huang R, Lv G, Zou Z, Jiang XC, Zou C, Liu W, Luo J, Zhao Z, Muhammad S, Wang G, Chen YG, Wang X. Role of miR-30a targeting insulin receptor substrate 2 in colorectal tumorigenesis. Mol Cell Biol. 2015;35:988–1000.CrossRefPubMedPubMedCentral Zhang Q, Tang Q, Qin D, Yu L, Huang R, Lv G, Zou Z, Jiang XC, Zou C, Liu W, Luo J, Zhao Z, Muhammad S, Wang G, Chen YG, Wang X. Role of miR-30a targeting insulin receptor substrate 2 in colorectal tumorigenesis. Mol Cell Biol. 2015;35:988–1000.CrossRefPubMedPubMedCentral
13.
go back to reference Lu N, Lin T, Wang L, Qi M, Liu Z, Dong H, Zhang X, Zhai C, Wang Y, Liu L, Xiang L, Qi L, Han B, Li J. Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma. Tumour Biol. 2015;36:3843–52.CrossRefPubMed Lu N, Lin T, Wang L, Qi M, Liu Z, Dong H, Zhang X, Zhai C, Wang Y, Liu L, Xiang L, Qi L, Han B, Li J. Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma. Tumour Biol. 2015;36:3843–52.CrossRefPubMed
15.
go back to reference Wu XR, He XS, Chen YF, Yuan RX, Zeng Y, Lian L, Zou YF, Lan N, Wu XJ, Lan P. High expression of CD73 as a poor prognostic biomarker in human colorectal cancer. J Surg Oncol. 2012;106:130–7.CrossRefPubMed Wu XR, He XS, Chen YF, Yuan RX, Zeng Y, Lian L, Zou YF, Lan N, Wu XJ, Lan P. High expression of CD73 as a poor prognostic biomarker in human colorectal cancer. J Surg Oncol. 2012;106:130–7.CrossRefPubMed
16.
go back to reference Allard B, Turcotte M, Stagg J. CD73-generated adenosine: orchestrating the tumor-stroma interplay to promote cancer growth. J Biomed Biotechnol. 2012;2012:485156.CrossRefPubMedPubMedCentral Allard B, Turcotte M, Stagg J. CD73-generated adenosine: orchestrating the tumor-stroma interplay to promote cancer growth. J Biomed Biotechnol. 2012;2012:485156.CrossRefPubMedPubMedCentral
17.
go back to reference Stagg J, Divisekera U, McLaughlin N, Sharkey J, Pommey S, Denoyer D, Dwyer KM, Smyth MJ. Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci U S A. 2010;107:1547–52.CrossRefPubMedPubMedCentral Stagg J, Divisekera U, McLaughlin N, Sharkey J, Pommey S, Denoyer D, Dwyer KM, Smyth MJ. Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci U S A. 2010;107:1547–52.CrossRefPubMedPubMedCentral
18.
go back to reference Allard B, Turcotte M, Spring K, Pommey S, Royal I, Stagg J. Anti-CD73 therapy impairs tumor angiogenesis. Int J Cancer. 2014;134:1466–73.CrossRefPubMed Allard B, Turcotte M, Spring K, Pommey S, Royal I, Stagg J. Anti-CD73 therapy impairs tumor angiogenesis. Int J Cancer. 2014;134:1466–73.CrossRefPubMed
20.
go back to reference Baraniskin A, Birkenkamp-Demtroder K, Maghnouj A, Zöllner H, Munding J, Klein-Scory S, Reinacher-Schick A, Schwarte-Waldhoff I, Schmiegel W, Hahn SA. MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL. Carcinogenesis. 2012;33:732–9.CrossRefPubMed Baraniskin A, Birkenkamp-Demtroder K, Maghnouj A, Zöllner H, Munding J, Klein-Scory S, Reinacher-Schick A, Schwarte-Waldhoff I, Schmiegel W, Hahn SA. MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL. Carcinogenesis. 2012;33:732–9.CrossRefPubMed
21.
go back to reference Liu XY, Tang QS, Chen HC, Jiang XL, Fang H. Lentiviral miR30-based RNA interference against heparanase suppresses melanoma metastasis with lower liver and lung toxicity. Int J Biol Sci. 2013;9:564–77.CrossRefPubMedPubMedCentral Liu XY, Tang QS, Chen HC, Jiang XL, Fang H. Lentiviral miR30-based RNA interference against heparanase suppresses melanoma metastasis with lower liver and lung toxicity. Int J Biol Sci. 2013;9:564–77.CrossRefPubMedPubMedCentral
22.
go back to reference Ouzounova M, Vuong T, Ancey PB, Ferrand M, Durand G, Le-Calvez KF, Croce C, Matar C, Herceg Z, Hernandez-Vargas H. MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells. BMC Genomics. 2013;14:139.CrossRefPubMedPubMedCentral Ouzounova M, Vuong T, Ancey PB, Ferrand M, Durand G, Le-Calvez KF, Croce C, Matar C, Herceg Z, Hernandez-Vargas H. MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells. BMC Genomics. 2013;14:139.CrossRefPubMedPubMedCentral
23.
go back to reference Lu XX, Chen YT, Feng B, Mao XB, Yu B, Chu XY. Expression and clinical significance of CD73 and hypoxia-inducible factor-1alpha in gastric carcinoma. World J Gastroenterol. 2013;19:1912–8.CrossRefPubMedPubMedCentral Lu XX, Chen YT, Feng B, Mao XB, Yu B, Chu XY. Expression and clinical significance of CD73 and hypoxia-inducible factor-1alpha in gastric carcinoma. World J Gastroenterol. 2013;19:1912–8.CrossRefPubMedPubMedCentral
24.
go back to reference Turcotte M, Spring K, Pommey S, Chouinard G, Cousineau I, George J, Chen GM, Gendoo DM, Haibe-Kains B, Karn T, Rahimi K, Le Page C, Provencher D, Mes-Masson AM, Stagg J. CD73 is associated with poor prognosis in high-grade serous ovarian cancer. Cancer Res. 2015;75:4494–503.CrossRefPubMed Turcotte M, Spring K, Pommey S, Chouinard G, Cousineau I, George J, Chen GM, Gendoo DM, Haibe-Kains B, Karn T, Rahimi K, Le Page C, Provencher D, Mes-Masson AM, Stagg J. CD73 is associated with poor prognosis in high-grade serous ovarian cancer. Cancer Res. 2015;75:4494–503.CrossRefPubMed
25.
go back to reference Leclerc BG, Charlebois R, Chouinard G, Allard B, Pommey S, Saad F, Stagg J. CD73 expression is an independent prognostic factor in prostate cancer. Clin Cancer Res. 2016;22:158–66.CrossRefPubMed Leclerc BG, Charlebois R, Chouinard G, Allard B, Pommey S, Saad F, Stagg J. CD73 expression is an independent prognostic factor in prostate cancer. Clin Cancer Res. 2016;22:158–66.CrossRefPubMed
26.
go back to reference Stagg J, Beavis PA, Divisekera U, Liu MC, Moller A, Darcy PK, Smyth MJ. CD73-deficient mice are resistant to carcinogenesis. Cancer Res. 2012;72:2190–6.CrossRefPubMed Stagg J, Beavis PA, Divisekera U, Liu MC, Moller A, Darcy PK, Smyth MJ. CD73-deficient mice are resistant to carcinogenesis. Cancer Res. 2012;72:2190–6.CrossRefPubMed
28.
go back to reference Salmi M, Jalkanen S. Homing-associated molecules CD73 and VAP-1 as targets to prevent harmful inflammations and cancer spread. FEBS Lett. 2011;585:1543–50.CrossRefPubMed Salmi M, Jalkanen S. Homing-associated molecules CD73 and VAP-1 as targets to prevent harmful inflammations and cancer spread. FEBS Lett. 2011;585:1543–50.CrossRefPubMed
30.
go back to reference Wang L, Fan J, Thompson LF, Zhang Y, Shin T, Curiel TJ, Zhang B. CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. J Clin Invest. 2011;121:2371–82.CrossRefPubMedPubMedCentral Wang L, Fan J, Thompson LF, Zhang Y, Shin T, Curiel TJ, Zhang B. CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. J Clin Invest. 2011;121:2371–82.CrossRefPubMedPubMedCentral
Metadata
Title
MicroRNA-30a regulates cell proliferation and tumor growth of colorectal cancer by targeting CD73
Authors
Minghao Xie
Huabo Qin
Qianxin Luo
Qunsheng Huang
Xiaosheng He
Zihuan Yang
Ping Lan
Lei Lian
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3291-8

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