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Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

Research Article

Multidimensional Integration Analysis of Autophagy-related Modules in Colorectal Cancer

Author(s): Yang Zhang, Zheng Zhang, Dong Wang, Jianzhen Xu, Yanhui Li, Hong Wang, Jin Li, Shaowen Mo, Yuncong Zhang, Yunqing Lin, Xiuzhao Fan, Enmin Li, Jian Huang*, Huihui Fan* and Ying Yi*

Volume 16, Issue 4, 2019

Page: [340 - 346] Pages: 7

DOI: 10.2174/1570178615666180914113224

Price: $65

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Abstract

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract occurring in the colon, which mainly divided into adenocarcinoma, mucinous adenocarcinoma, and undifferentiated carcinoma. However, autophagy is related to the occurrence and development of various kinds of human diseases such as cancer. There is little research on the relationship between CRC and autophagy. Hence, we performed multidimensional integration analysis to systematically explore potential relationship between autophagy and CRC. Based on gene expression datasets of colon adenocarcinoma (COAD) and protein-protein interactions (PPIs), we first identified 12 autophagy-related modules in COAD using WGCNA. Then, 9 module pairs which with significantly crosstalk were deciphered, a total of 6 functional modules. Autophagy-related genes in these modules were closely related with CRC, emphasizing that the important role of autophagy-related genes in CRC, including PPP2CA and EIF4E, etc. In addition to, by integrating transcription factor (TF)-target and RNA-associated interactions, a regulation network was constructed, in which 42 TFs (including SMAD3 and TP53, etc.) and 20 miRNAs (including miR-20 and miR-30a, etc.) were identified as pivot regulators. Pivot TFs were mainly involved in cell cycle, cell proliferation and pathways in cancer. And pivot miRNAs were demonstrated associated with CRC. It suggests that these pivot regulators might be have an effect on the development of CRC by regulating autophagy. In a word, our results suggested that multidimensional integration strategy provides a novel approach to discover potential relationships between autophagy and CRC, and further improves our understanding of autophagy and tumor in human.

Keywords: Colorectal cancer, autophagy, co-expression modules, multidimensional analysis, COAD, WGCNA.

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[1]
Mattar, M.C.; Lough, D.; Pishvaian, M.J.; Charabaty, A. Gastrointest. Cancer Res., 2011, 4, 53-61.
[2]
Winawer, S.; Fletcher, R.; Rex, D.; Bond, J.; Burt, R.; Ferrucci, J.; Ganiats, T.; Levin, T.; Woolf, S.; Johnson, D.; Kirk, L.; Litin, S.; Simmang, C. Gastroenterology, 2003, 124, 544-560.
[3]
Guan, X.; Yi, Y.; Huang, Y.; Hu, Y.; Li, X.; Wang, X.; Fan, H.; Wang, G.; Wang, D. Oncotarget, 2015, 6, 37600-37612.
[4]
Jin, S.; White, E. Autophagy, 2007, 3, 28-31.
[5]
Gozuacik, D.; Kimchi, A. Oncogene, 2004, 23, 2891-2906.
[6]
Takamura, A.; Komatsu, M.; Hara, T.; Sakamoto, A.; Kishi, C.; Waguri, S.; Eishi, Y.; Hino, O.; Tanaka, K.; Mizushima, N. Genes Dev., 2011, 25, 795-800.
[7]
Rao, S.; Tortola, L.; Perlot, T.; Wirnsberger, G.; Novatchkova, M.; Nitsch, R.; Sykacek, P.; Frank, L.; Schramek, D.; Komnenovic, V.; Sigl, V.; Aumayr, K.; Schmauss, G.; Fellner, N.; Handschuh, S.; Glosmann, M.; Pasierbek, P.; Schlederer, M.; Resch, G.P.; Ma, Y.; Yang, H.; Popper, H.; Kenner, L.; Kroemer, G.; Penninger, J.M. Nat. Commun., 2014, 5, 3056.
[8]
Lee, H.W.; Jang, K.S.; Choi, H.J.; Jo, A.; Cheong, J.H.; Chun, K.H. BMB Rep., 2014, 47, 697-702.
[9]
Donohoe, D.R.; Garge, N.; Zhang, X.; Sun, W.; O’Connell, T.M.; Bunger, M.K.; Bultman, S.J. Cell Metab., 2011, 13, 517-526.
[10]
Heras-Sandoval, D.; Perez-Rojas, J.M.; Hernandez-Damian, J.; Pedraza-Chaverri, J. Cell. Signal., 2014, 26, 2694-2701.
[11]
Saiki, S.; Sasazawa, Y.; Imamichi, Y.; Kawajiri, S.; Fujimaki, T.; Tanida, I.; Kobayashi, H.; Sato, F.; Sato, S.; Ishikawa, K.; Imoto, M.; Hattori, N. Autophagy, 2011, 7, 176-187.
[12]
Shimizu, S.; Kanaseki, T.; Mizushima, N.; Mizuta, T.; Arakawa-Kobayashi, S.; Thompson, C.B.; Tsujimoto, Y. Nat. Cell Biol., 2004, 6, 1221-1228.
[13]
Levine, B.; Sinha, S.C.; Kroemer, G. Autophagy, 2008, 4, 600-606.
[14]
Yue, Z.; Jin, S.; Yang, C.; Levine, A.J.; Heintz, N. Proc. Natl. Acad. Sci. USA, 2003, 100, 15077-15082.
[15]
Marino, G.; Salvador-Montoliu, N.; Fueyo, A.; Knecht, E.; Mizushima, N.; Lopez-Otin, C. J. Biol. Chem., 2007, 282, 18573-18583.
[16]
Choi, M.S.; Kim, Y.; Jung, J.Y.; Yang, S.H.; Lee, T.R.; Shin, D.W. Exp. Dermatol., 2013, 22, 491-494.
[17]
Ueno, T.; Sato, W.; Horie, Y.; Komatsu, M.; Tanida, I.; Yoshida, M.; Ohshima, S.; Mak, T.W.; Watanabe, S.; Kominami, E. Autophagy, 2008, 4, 692-700.
[18]
Homma, K.; Suzuki, K.; Sugawara, H. Nucleic Acids Res., 2011, 39, D986-D990.
[19]
Turei, D.; Foldvari-Nagy, L.; Fazekas, D.; Modos, D.; Kubisch, J.; Kadlecsik, T.; Demeter, A.; Lenti, K.; Csermely, P.; Vellai, T.; Korcsmaros, T. Autophagy, 2015, 11, 155-165.
[20]
Tomczak, K.; Czerwinska, P.; Wiznerowicz, M. Contemp. Oncol. (Pozn.), 2015, 19, A68-A77.
[21]
Pinero, J.; Bravo, A.; Queralt-Rosinach, N.; Gutierrez-Sacristan, A.; Deu-Pons, J.; Centeno, E.; Garcia-Garcia, J.; Sanz, F.; Furlong, L.I. Nucleic Acids Res., 2017, 45, D833-D839.
[22]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. Nucleic Acids Res., 2017, 45, D362-D368.
[23]
Yu, Y.; Liu, H.; Jin, M.; Zhang, M.; Pan, Y.; Zhang, S.; Li, Q.; Chen, K. Ann. Hum. Genet., 2012, 76, 269-276.
[24]
Karban, A.S.; Okazaki, T.; Panhuysen, C.I.; Gallegos, T.; Potter, J.J.; Bailey-Wilson, J.E.; Silverberg, M.S.; Duerr, R.H.; Cho, J.H.; Gregersen, P.K.; Wu, Y.; Achkar, J.P.; Dassopoulos, T.; Mezey, E.; Bayless, T.M.; Nouvet, F.J.; Brant, S.R. Hum. Mol. Genet., 2004, 13, 35-45.
[25]
Loo, L.W.; Tiirikainen, M.; Cheng, I.; Lum-Jones, A.; Seifried, A.; Church, J.M.; Gryfe, R.; Weisenberger, D.J.; Lindor, N.M.; Gallinger, S.; Haile, R.W.; Duggan, D.J.; Thibodeau, S.N.; Casey, G.; Le Marchand, L. Genes Chromosomes Cancer, 2013, 52, 450-466.
[26]
Yuan, Q.; Li, P.D.; Li, B.H.; Yang, X.Z.; Xu, S.B.; Liu, X.H.; Zhou, F.X.; Zhang, W.J. J. Cancer Res. Clin. Oncol., 2009, 135, 131-140.
[27]
Slattery, M.L.; Lundgreen, A.; Herrick, J.S.; Wolff, R.K.; Caan, B.J. Cancer, 2011, 117, 4175-4183.
[28]
Slattery, M.L.; Herrick, J.S.; Lundgreen, A.; Wolff, R.K. Cancer Epidemiol. Biomarkers Prev., 2011, 20, 57-69.
[29]
Rhoads, R.E. Curr. Opin. Cell Biol., 1991, 3, 1019-1024.
[30]
Golob-Schwarzl, N.; Schweiger, C.; Koller, C.; Krassnig, S.; Gogg-Kamerer, M.; Gantenbein, N.; Toeglhofer, A.M.; Wodlej, C.; Bergler, H.; Pertschy, B.; Uranitsch, S.; Holter, M.; El-Heliebi, A.; Fuchs, J.; Punschart, A.; Stiegler, P.; Keil, M.; Hoffmann, J.; Henderson, D.; Lehrach, H.; Reinhard, C.; Regenbrecht, C.; Schicho, R.; Fickert, P.; Lax, S.; Haybaeck, J. Oncotarget, 2017, 8, 101224-101243.
[31]
Chevrier, S.; Arnould, L.; Ghiringhelli, F.; Coudert, B.; Fumoleau, P.; Boidot, R. Int. J. Oncol., 2014, 45, 1167-1174.
[32]
Irahara, N.; Baba, Y.; Nosho, K.; Shima, K.; Yan, L.; Dias-Santagata, D.; Iafrate, A.J.; Fuchs, C.S.; Haigis, K.M.; Ogino, S. Diagn. Mol. Pathol., 2010, 19, 157-163.
[33]
Takagi, Y.; Futamura, M.; Yamaguchi, K.; Aoki, S.; Takahashi, T.; Saji, S. Gut, 2000, 47, 268-271.
[34]
Bakirtzi, K.; Hatziapostolou, M.; Karagiannides, I.; Polytarchou, C.; Jaeger, S.; Iliopoulos, D.; Pothoulakis, C. Gastroenterology, 2011, 141, 1749-1761 e1741.
[35]
Thangaraju, M.; Carswell, K.N.; Prasad, P.D.; Ganapathy, V. Biochem. J., 2009, 417, 379-389.
[36]
Zeestraten, E.C.; Maak, M.; Shibayama, M.; Schuster, T.; Nitsche, U.; Matsushima, T.; Nakayama, S.; Gohda, K.; Friess, H.; van de Velde, C.J.; Ishihara, H.; Rosenberg, R.; Kuppen, P.J.; Janssen, K.P. Br. J. Cancer, 2012, 106, 133-140.
[37]
Nomoto, K.; Tomita, N.; Miyake, M.; Xhu, D.B.; LoGerfo, P.R.; Weinstein, I.B. Mol. Carcinog., 1995, 12, 146-152.
[38]
Irby, R.B.; Mao, W.; Coppola, D.; Kang, J.; Loubeau, J.M.; Trudeau, W.; Karl, R.; Fujita, D.J.; Jove, R.; Yeatman, T.J. Nat. Genet., 1999, 21, 187-190.
[39]
Hong, S.W.; Kim, S.M.; Jin, D.H.; Kim, Y.S.; Hur, D.Y. Biochem. Biophys. Res. Commun., 2017, 491, 303-309.
[40]
Lee, S.; Bang, S.; Song, K.; Lee, I. Oncol. Rep., 2006, 16, 747-754.
[41]
Wang, H.; Yu, J.; Zhang, L.; Xiong, Y.; Chen, S.; Xing, H.; Tian, Z.; Tang, K.; Wei, H.; Rao, Q.; Wang, M.; Wang, J. Biochem. Biophys. Res. Commun., 2014, 446, 1204-1210.
[42]
Tsoi, H.; Lam, K.C.; Dong, Y.; Zhang, X.; Lee, C.K.; Zhang, J.; Ng, S.C.; Ng, S.S.M.; Zheng, S.; Chen, Y.; Fang, J.; Yu, J. Oncogene, 2017, 36, 6109-6118.
[43]
Lu, B.; Xu, J.; Zhu, Y.; Zhang, H.; Lai, M. Clin. Chim. Acta, 2007, 378, 42-47.
[44]
Han, H.; Cho, J.W.; Lee, S.; Yun, A.; Kim, H.; Bae, D.; Yang, S.; Kim, C.Y.; Lee, M.; Kim, E.; Lee, S.; Kang, B.; Jeong, D.; Kim, Y.; Jeon, H.N.; Jung, H.; Nam, S.; Chung, M.; Kim, J.H.; Lee, I. Nucleic Acids Res., 2018, 46, D380-D386.
[45]
Wu, D.; Huang, Y.; Kang, J.; Li, K.; Bi, X.; Zhang, T.; Jin, N.; Hu, Y.; Tan, P.; Zhang, L.; Yi, Y.; Shen, W.; Huang, J.; Li, X.; Li, X.; Xu, J.; Wang, D. Autophagy, 2015, 11, 1917-1926.
[46]
Jiang, Q.; Wang, Y.; Hao, Y.; Juan, L.; Teng, M.; Zhang, X.; Li, M.; Wang, G.; Liu, Y. Nucleic Acids Res., 2009, 37, D98-D104.
[47]
Vial, E.; Marshall, C.J. J. Cell Sci., 2003, 116, 4957-4963.
[48]
Groulx, J.F.; Khalfaoui, T.; Benoit, Y.D.; Bernatchez, G.; Carrier, J.C.; Basora, N.; Beaulieu, J.F. Autophagy, 2012, 8, 893-902.
[49]
Balakumaran, B.S.; Porrello, A.; Hsu, D.S.; Glover, W.; Foye, A.; Leung, J.Y.; Sullivan, B.A.; Hahn, W.C.; Loda, M.; Febbo, P.G. Cancer Res., 2009, 69, 7803-7810.
[50]
Xie, X.; Le, L.; Fan, Y.; Lv, L.; Zhang, J. Autophagy, 2012, 8, 1071-1084.
[51]
Liu, F.L.; Mo, E.P.; Yang, L.; Du, J.; Wang, H.S.; Zhang, H.; Kurihara, H.; Xu, J.; Cai, S.H. Oncotarget, 2016, 7, 4122-4141.
[52]
Motoyama, K.; Inoue, H.; Takatsuno, Y.; Tanaka, F.; Mimori, K.; Uetake, H.; Sugihara, K.; Mori, M. Int. J. Oncol., 2009, 34, 1069-1075.
[53]
Chai, H.; Liu, M.; Tian, R.; Li, X.; Tang, H. Acta Biochim. Biophys. Sin. (Shanghai), 2011, 43, 217-225.
[54]
Baraniskin, A.; Birkenkamp-Demtroder, K.; Maghnouj, A.; Zollner, H.; Munding, J.; Klein-Scory, S.; Reinacher-Schick, A.; Schwarte-Waldhoff, I.; Schmiegel, W.; Hahn, S.A. Carcinogenesis, 2012, 33, 732-739.
[55]
Wei, W.; Yang, Y.; Cai, J.; Cui, K.; Li, R.X.; Wang, H.; Shang, X.; Wei, D. Cell. Physiol. Biochem., 2016, 39, 1165-1176.
[56]
Zhong, M.; Bian, Z.; Wu, Z. Cell. Physiol. Biochem., 2013, 31, 209-218.
[57]
Cui, T.; Zhang, L.; Huang, Y.; Yi, Y.; Tan, P.; Zhao, Y.; Hu, Y.; Xu, L.; Li, E.; Wang, D. Nucleic Acids Res., 2018, 46, D371-D374.
[58]
Zhang, T.; Tan, P.; Wang, L.; Jin, N.; Li, Y.; Zhang, L.; Yang, H.; Hu, Z.; Zhang, L.; Hu, C.; Li, C.; Qian, K.; Zhang, C.; Huang, Y.; Li, K.; Lin, H.; Wang, D. Nucleic Acids Res., 2017, 45, D135-D138.
[59]
Yi, Y.; Zhao, Y.; Li, C.; Zhang, L.; Huang, H.; Li, Y.; Liu, L.; Hou, P.; Cui, T.; Tan, P.; Hu, Y.; Zhang, T.; Huang, Y.; Li, X.; Yu, J.; Wang, D. Nucleic Acids Res., 2017, 45, D115-D118.
[60]
Li, Y.; Wang, C.; Miao, Z.; Bi, X.; Wu, D.; Jin, N.; Wang, L.; Wu, H.; Qian, K.; Li, C.; Zhang, T.; Zhang, C.; Yi, Y.; Lai, H.; Hu, Y.; Cheng, L.; Leung, K.S.; Li, X.; Zhang, F.; Li, K.; Li, X.; Wang, D. Nucleic Acids Res., 2015, 43, D578-D582.
[61]
Qi, J.; Dong, Z.; Liu, J.; Zhang, J.T. Oncogene, 2014, 33, 4156-4163.
[62]
Rho, J.H.; Qin, S.; Wang, J.Y.; Roehrl, M.H. J. Proteome Res., 2008, 7, 2959-2972.
[63]
Langfelder, P.; Horvath, S. BMC Bioinformatics, 2008, 9, 559.
[64]
Milo, R.; Shen-Orr, S.; Itzkovitz, S.; Kashtan, N.; Chklovskii, D.; Alon, U. Science, 2002, 298, 824-827.
[65]
Zhang, H.M.; Liu, T.; Liu, C.J.; Song, S.; Zhang, X.; Liu, W.; Jia, H.; Xue, Y.; Guo, A.Y. Nucleic Acids Res., 2015, 43, D76-D81.
[66]
Ulitsky, I.; Shamir, R. Mol. Syst. Biol., 2007, 3, 104.
[67]
Huang da. W.; Sherman, B.T.; Lempicki, R.A. Nucleic Acids Res., 2009, 37, 1-13.

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