An integrative framework to identify cell death-related microRNAs in esophageal squamous cell carcinoma

// Bing-Li Wu 1, 3, * , Dong Wang 1, 6, * , Wen-Jing Bai 1, 3 , Fan Zhang 5 , Xing Zhao 5 , Ying Yi 6 , Ting Zhang 6 , Wen-Jun Shen 5 , En-Min Li 1, 3 , Li-Yan Xu 1, 4 , Jian-Zhen Xu 1, 2, 5 1 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China 2 Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA 3 Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China 4 Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China 5 Department of Bioinformatics, Shantou University Medical College, Shantou 515041, China 6 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China * These authors have contributed equally to this work Correspondence to: En-Min Li, email: nmli@stu.edu.cn Li-Yan Xu, email: lyxu@stu.edu.cn Jian-Zhen Xu, email: xujz0451@xsgmail.com Keywords: autophagy, apoptosis, cell death, miRNA, esophageal squamous cell carcinoma Abbreviations: ESCC: esophageal squamous cell carcinoma, GO: gene ontology, SQSTM1/P62: sequestosome 1, PARP: poly (ADP-ribose) polymerase 1, LC3: microtubule-associated protein 1 light chain 3 Received: November 29, 2015 Accepted: July 06, 2016 Published: July 22, 2016 ABSTRACT Cell death is a critical biological process involved in many important functions, and defects in this system are usually linked with numerous human diseases including cancers. Esophageal squamous cell carcinoma is one of the most chemo- and biological therapy resistant cancers. Based on knowledge repository and four miRNAs profiling data, we proposed a general framework to hunt for cell death miRNAs in a context dependent manner. We predicted 12 candidate miRNAs from hundreds of others. Follow-up experimental verification of 7 miRNAs indicated at least 3 miRNAs (MIR20b, MIR498 and MIR196) were involved in both apoptosis and autophagy processes. These results indicated miRNAs intimately connected the two cell death modules in esophageal squamous cell carcinoma. This integrative framework can also be easily extended to identify miRNAs in other key cellular signaling pathways or may find conditional specific miRNAs in other cancer types.