title: MicroRNA-224 is implicated in lung cancer pathogenesis through targeting caspase-3 and caspase-7.
abstract: We recently reported that miR-224 was significantly up-regulated in non-small cell lung cancer (NSCLC) tissues, in particular in resected NSCLC metastasis. We further demonstrated that miR-224 functions as an oncogene in NSCLC by directly targeting TNFAIP1 and SMAD4. However, the biological functions of miR-224 in NSCLC are controversial and underlying mechanisms of miR-224 in the progression and metastasis of lung cancer remain to be further explored. Here we report that caspase3 (CASP3) and caspase7 (CASP7) are previously unidentified targets of miR-224 in NSCLC, and that miR-224 promotes lung cancer cells proliferation and migration in part by directly targeting CASP7 and down-regulating its expression. In addition, miR-224 attenuated TNF-α induced apoptosis by direct targeting of CASP3 resulting in reduction of cleaved PARP1 expression in lung cancer cells. Furthermore, the expression of miR-224 negatively correlates with the expression of CASP7 and CASP3 in tissue samples from patients with lung cancer. Finally, we found that activated NF-κB signaling is involved in the regulation of miR-224 expression in lung cancer. Our study provides new insight in understanding of oncogenic role of miR-224 in the lung cancer pathogenesis and suggests that NF-κB/miR-224/CASP3, 7 pathway could be a putative therapeutic target in lung cancer.
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Chemical Biology Research Center, School of Pharmaceutical Sciences and Lung Cancer Research Center, The Zhoushan Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Ri
authors: R
authors: Cui
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Taewan
authors: T
authors: Kim
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Department of Medicine (DIMED), University of Padua, Padua, Italy.
authors: Matteo
authors: M
authors: Fassan
authors: Department of Radiation Oncology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Wei
authors: W
authors: Meng
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Hui-Lung
authors: HL
authors: Sun
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Young-Jun
authors: YJ
authors: Jeon
authors: Applied Research on Cancer Network (ARC-NET) Research Centre, University of Verona, Verona, Italy.
authors: Caterina
authors: C
authors: Vicentini
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Department of Anesthesiology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors: Esmerina
authors: E
authors: Tili
authors: Division of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, China.
authors: Yong
authors: Y
authors: Peng
authors: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors: Aldo
authors: A
authors: Scarpa
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Guang
authors: G
authors: Liang
authors: Department of Cardio-Thoracic Surgery, Lung Cancer Research Center, Zhoushan Hospital of Wenzhou Medical University, Zhoushan, Zhejiang, China.
authors: Yong Kui
authors: YK
authors: Zhang
authors: Department of Radiation Oncology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Arnab
authors: A
authors: Chakravarti
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Carlo M
authors: CM
authors: Croce
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7
keywords: caspase-3; caspase-7; lung cancer; miR-224