Overexpress Ovol2 Gene Inhibiting the Migration and Invasion Ability of Lung Adeno-carcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANGZhi-hai ¹ , LIZhong ¹ , YANGQing-jie ² , GUOMing ²

1. Department of Cardiothoracic Surgery, PLA 174 th Clinical College of Anhui Medical University, Xiamen 361000 Fujian, P. R. China;
2. Department of Cardiothoracic Surgery, The Success Hospital Affiliated Xiamen University, Xiamen 361000 Fujian, P. R. China;

Corresponding author：

Keywords：

Ovol2 gene; Epithelial-mesenchymal transition (EMT); Lung adenocarcinoma; Distant metastasis; Migration

DOI：

10.7507/1007-4848.20160038

Video：

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Objective To explore the effectiveness of Ovol2 gene for epithelial-mesenchymal transition (EMT) to offer some theory evidences for the targeted therapy in lung adenocarcinoma. Methods A549 cells were treated with control and Ovol2 overexpressioned by lentivirus infection. Real-time PCR were performed to test the mRNA level of genes correlated to EMT. Western Blot was performed for protein level of the following makers:E-cadherin, N-cadherin, vimentin, ect. Moreover, we tested the migration and invasion ability of A549 cells by transwell and wound healing experiment. Results After treated with Ovol2 overexpressed, the expression level of E-cadherin raised, while the expression level of N-cadherin, vimentin and Twist1 declined in both mRNA and protein expression level. The results of wound healing and transwell experiment indicated that the migration and invasion ability of A549 cells weakened. Conclusion Overexpression of Ovol2 gene can suppress the distant metastasis ability and invasion ability of A549 cells by inhibiting the EMT.

Citation： WANGZhi-hai, LIZhong, YANGQing-jie, GUOMing. Overexpress Ovol2 Gene Inhibiting the Migration and Invasion Ability of Lung Adeno-carcinoma. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(2): 173-177. doi: 10.7507/1007-4848.20160038 Copy

1.	Garfinkel MD, Wang J, Liang Y, et al. Multiple products from the shavenbaby-ovo gene region of Drosophila melanogaster: relationship to genetic complexity. Mol Cell Biol, 1994, 14(10): 6809-6818.
2.	Mevel-Ninio M, Terracol R, Kafatos FC. The ovo gene of Drosop-hilaencodes a zinc finger protein required for female germ line development. Embo J, 1991, 10(8): 2259-2266.
3.	Mackay DR, Hu M, Li B, et al. The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol, 2006, 291(1): 38-52.
4.	Unezaki S, Horai R, Sudo K, et al. Ovol2/Movo, a homologue of Drosophila ovo, is required for angiogenesis, heart formation and placental development in mice. Genes Cells, 2007, 12(6): 773-785.
5.	Zhang T, Zhu Q, Xie Z, et al. The zinc finger transcription factor Ovol2 acts downstream of the bone morphogenetic protein pathway to regulate the cell fate decision between neuroectoderm and mesendoderm. J Bio Chem, 2013, 288(9): 6166-6177.
6.	Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest, 2003, 112(12): 1776-1784.
7.	Nieto MA. The ins and outs of the epithelial to mesenchymal transi-tion in health and disease. Ann Rev Cell Dev Biol, 2011, 27: 347-376.
8.	Acloque H, Ocañ a OH, Matheu A, et al. Reciprocal repression between Sox3 and snail transcription factors defines embryonic territories at gastrulation. Dev Cell, 2011, 21(3): 546-558.
9.	Roca H, Hernandez J, Weidner S, et al. Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer. PloS one, 2013, 8(10): e76773.
10.	Thiery JP, Acloque H, Huang RYJ, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5): 871-890.
11.	Watanabe K, Villarreal-Ponce A, Sun P, et al. Mammary morpho-genesis and regeneration require the inhibition of EMT at terminal end buds by ovol2 transcriptional repressor. Dev Cell, 2014, 29(1): 59-74.
12.	Cavallaro U, Schaffhauser B, Christofori G. Cadherins and the tumour progression: is it all in a switch? Cancer Lett, 2002, 176(2): 123-128.
13.	Christofori G, Semb H. The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci 1999, 24(2): 73-76.
14.	孙威.非小细胞肺癌治疗进展.中华现代外科学杂志, 2005, 2(1): 75-78.
15.	王珏, 郭占领.Ⅰ期至ⅢA期肺癌外科规范化治疗的研究进展.中国胸心血管外科临床杂志, 2014, 21(5): 675-680.
16.	Verdecchia A, Francisci S, Brenner H, et al. Recent cancer survival in Europe: a 2000-2002 period analysis of EUROCARE-4 data. Lancet Oncol, 2007, 8(9): 784-796.
17.	Gupta GP, Massagué J. Cancer metastasis: building a framework. Cell, 2006, 127(4): 679-695.
18.	Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol, 2006, 7(2): 131-142.
19.	Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, et al. Metformin against TGFβ-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle, 2010, 9(22): 4461-4468.
20.	Li L, Li W. Epithelial-mesenchymal transition in human cancer: Comprehensive reprogramming of metabolism, epigenetics, and differentiation. Pharmacol Ther, 2015, 150: 33-46.
21.	Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3' kinase/AKT pathways. Oncogene, 2005, 24(50): 7443-7454.
22.	Mackay DR, Hu M, Li B, et al. The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol, 2006, 291(1): 38-52.
23.	Payre F, Vincent A, Carreno S. Ovo/svb integrates Wingless and DER pathways to control epidermis differentiation. Nature, 1999, 400(6741): 271-275.
24.	Christina S, Elinor Ng E, Sophia Hsin-Jung L, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell, 2011, 145(6): 926-940.
25.	Watanabe K, Villarreal-Ponce A, Sun P. Mammary morphogenesis and regeneration require the inhibition of EMT at terminal end buds by Ovol2transcriptional repressor. Dev Cell, 2014, 29(1): 59-74.
26.	吴跃超. Ovol2在人乳腺癌细胞中抑制TGF-b信号通路的分子机制研究.厦门大学:厦门大学学位论文. 2014.
27.	田茗源, 王林辉, 张雄, 等.肺癌组织中E-cadherin和Vimentin的表达及其与上皮-间质转化的相关性.中国生物制品学杂志, 2011, 24(9): 1068-1071.
28.	郭凯, 王晓东.肺癌组织中EMT相关蛋白的表达变化及意义[J].山东医药, 2012, 52(2): 70-71.
29.	黄振杰, 郑金旭, 汤艳, 等.肺泡上皮细胞间质转化对肺癌细胞转移影响的研究.中华肿瘤防治杂志, 2011, 18(16): 1230-1234.
30.	李洪利, 尹崇高, 李文通, 等.过表达Snail增强肺癌细胞A549的体外侵袭能力.中国生物化学与分子生物学报, 2010, 10: 943-948.
31.	孙菊杰, 魏玲, 张德贤, 等.非小细胞肺癌Twist表达与EMT相关性分析.中华肿瘤防治杂志, 2014, 21(16): 13.

1. Garfinkel MD, Wang J, Liang Y, et al. Multiple products from the shavenbaby-ovo gene region of Drosophila melanogaster: relationship to genetic complexity. Mol Cell Biol, 1994, 14(10): 6809-6818.
2. Mevel-Ninio M, Terracol R, Kafatos FC. The ovo gene of Drosop-hilaencodes a zinc finger protein required for female germ line development. Embo J, 1991, 10(8): 2259-2266.
3. Mackay DR, Hu M, Li B, et al. The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol, 2006, 291(1): 38-52.
4. Unezaki S, Horai R, Sudo K, et al. Ovol2/Movo, a homologue of Drosophila ovo, is required for angiogenesis, heart formation and placental development in mice. Genes Cells, 2007, 12(6): 773-785.
5. Zhang T, Zhu Q, Xie Z, et al. The zinc finger transcription factor Ovol2 acts downstream of the bone morphogenetic protein pathway to regulate the cell fate decision between neuroectoderm and mesendoderm. J Bio Chem, 2013, 288(9): 6166-6177.
6. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest, 2003, 112(12): 1776-1784.
7. Nieto MA. The ins and outs of the epithelial to mesenchymal transi-tion in health and disease. Ann Rev Cell Dev Biol, 2011, 27: 347-376.
8. Acloque H, Ocañ a OH, Matheu A, et al. Reciprocal repression between Sox3 and snail transcription factors defines embryonic territories at gastrulation. Dev Cell, 2011, 21(3): 546-558.
9. Roca H, Hernandez J, Weidner S, et al. Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer. PloS one, 2013, 8(10): e76773.
10. Thiery JP, Acloque H, Huang RYJ, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5): 871-890.
11. Watanabe K, Villarreal-Ponce A, Sun P, et al. Mammary morpho-genesis and regeneration require the inhibition of EMT at terminal end buds by ovol2 transcriptional repressor. Dev Cell, 2014, 29(1): 59-74.
12. Cavallaro U, Schaffhauser B, Christofori G. Cadherins and the tumour progression: is it all in a switch? Cancer Lett, 2002, 176(2): 123-128.
13. Christofori G, Semb H. The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci 1999, 24(2): 73-76.
14. 孙威.非小细胞肺癌治疗进展.中华现代外科学杂志, 2005, 2(1): 75-78.
15. 王珏, 郭占领.Ⅰ期至ⅢA期肺癌外科规范化治疗的研究进展.中国胸心血管外科临床杂志, 2014, 21(5): 675-680.
16. Verdecchia A, Francisci S, Brenner H, et al. Recent cancer survival in Europe: a 2000-2002 period analysis of EUROCARE-4 data. Lancet Oncol, 2007, 8(9): 784-796.
17. Gupta GP, Massagué J. Cancer metastasis: building a framework. Cell, 2006, 127(4): 679-695.
18. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol, 2006, 7(2): 131-142.
19. Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, et al. Metformin against TGFβ-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle, 2010, 9(22): 4461-4468.
20. Li L, Li W. Epithelial-mesenchymal transition in human cancer: Comprehensive reprogramming of metabolism, epigenetics, and differentiation. Pharmacol Ther, 2015, 150: 33-46.
21. Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3' kinase/AKT pathways. Oncogene, 2005, 24(50): 7443-7454.
22. Mackay DR, Hu M, Li B, et al. The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol, 2006, 291(1): 38-52.
23. Payre F, Vincent A, Carreno S. Ovo/svb integrates Wingless and DER pathways to control epidermis differentiation. Nature, 1999, 400(6741): 271-275.
24. Christina S, Elinor Ng E, Sophia Hsin-Jung L, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell, 2011, 145(6): 926-940.
25. Watanabe K, Villarreal-Ponce A, Sun P. Mammary morphogenesis and regeneration require the inhibition of EMT at terminal end buds by Ovol2transcriptional repressor. Dev Cell, 2014, 29(1): 59-74.
26. 吴跃超. Ovol2在人乳腺癌细胞中抑制TGF-b信号通路的分子机制研究.厦门大学:厦门大学学位论文. 2014.
27. 田茗源, 王林辉, 张雄, 等.肺癌组织中E-cadherin和Vimentin的表达及其与上皮-间质转化的相关性.中国生物制品学杂志, 2011, 24(9): 1068-1071.
28. 郭凯, 王晓东.肺癌组织中EMT相关蛋白的表达变化及意义[J].山东医药, 2012, 52(2): 70-71.
29. 黄振杰, 郑金旭, 汤艳, 等.肺泡上皮细胞间质转化对肺癌细胞转移影响的研究.中华肿瘤防治杂志, 2011, 18(16): 1230-1234.
30. 李洪利, 尹崇高, 李文通, 等.过表达Snail增强肺癌细胞A549的体外侵袭能力.中国生物化学与分子生物学报, 2010, 10: 943-948.
31. 孙菊杰, 魏玲, 张德贤, 等.非小细胞肺癌Twist表达与EMT相关性分析.中华肿瘤防治杂志, 2014, 21(16): 13.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Overexpress Ovol2 Gene Inhibiting the Migration and Invasion Ability of Lung Adeno-carcinoma

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