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|Title:||MicroRNA-224 is implicated in lung cancer pathogenesis through targeting caspase-3 and caspase-7||Authors:||Cui, Ri
Zhang, Yong Kui
Croce, Carlo M
|Keywords:||caspase-3;caspase-7;lung cancer;miR-224||Keywords Plus:||HEPATOCELLULAR-CARCINOMA;PROSTATE-CANCER;DOWN-REGULATION;BREAST-CANCER;UP-REGULATION;EXPRESSION;APOPTOSIS;ACTIVATION;MUTATIONS;MECHANISM||Mesh headings:||Carcinoma, Non-Small-Cell Lung;Caspase 3;Caspase 7;Gene Expression Regulation, Enzymologic;Gene Expression Regulation, Neoplastic;Lung Neoplasms;MicroRNAs||Secondary Mesh headings:||3' Untranslated Regions;Apoptosis;Blotting, Western;Cell Movement;Cell Proliferation;Humans;Immunoenzyme Techniques;NF-kappa B;Neoplasm Invasiveness;RNA, Messenger;Real-Time Polymerase Chain Reaction;Reverse Transcriptase Polymerase Chain Reaction;Tumor Cells, Cultured;Tumor Necrosis Factor-alpha||Issue Date:||8-Sep-2015||Publisher:||IMPACT JOURNALS LLC||Journal:||Oncotarget||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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