Priority Research Papers:
MicroRNA-224 is implicated in lung cancer pathogenesis through targeting caspase-3 and caspase-7
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Abstract
Ri Cui1,4,*, Taewan Kim2,*, Matteo Fassan1,3, Wei Meng5, Hui-Lung Sun1, Young-Jun Jeon1, Caterina Vicentini6, Esmerina Tili1,7, Yong Peng8, Aldo Scarpa9, Guang Liang10, Yong Kui Zhang11, Arnab Chakravarti5 and Carlo M. Croce1
1 Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
2 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 Department of Medicine (DIMED), University of Padua, Padua, Italy
4 Chemical Biology Research Center, School of Pharmaceutical Sciences, and Lung Cancer Research Center, The Zhoushan Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
5 Department of Radiation Oncology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
6 Applied Research on Cancer Network (ARC-NET) Research Centre, University of Verona, Verona, Italy
7 Department of Anesthesiology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
8 Division of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, China
9 Department of Pathology and Diagnostics, University of Verona, Verona, Italy
10 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
11 Department of Cardio-Thoracic Surgery, Lung Cancer Research Center, Zhoushan Hospital of Wenzhou Medical University, Zhoushan, Zhejiang, China
* These authors have contributed equally to this work
Correspondence to:
Carlo M. Croce, email:
Yong Peng, email:
Keywords: miR-224, lung cancer, caspase-3, caspase-7
Received: July 23, 2015 Accepted: August 08, 2015 Published: August 19, 2015
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.
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