miR-23a/b promote tumor growth and suppress apoptosis by targeting PDCD4 in gastric cancer
| Autor: | Xi Chen, Dongxia Hou, Weijie Zhang, Jia-Yi Cui, Ruichi Zhu, Ke Zen, Zhen Zhou, Hongwei Liang, Chen-Yu Zhang, Yanbo Wang, Qian Fan, Xiuting Hu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Carcinogenesis Immunology Apoptosis Biology Mice 03 medical and health sciences Cellular and Molecular Neuroscience Downregulation and upregulation Stomach Neoplasms Cell Line Tumor microRNA medicine Animals Humans Cell Proliferation Regulation of gene expression RNA-Binding Proteins Cancer Cell Biology medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Cell culture Cancer cell Cancer research Original Article Apoptosis Regulatory Proteins |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2017.447 |
| Popis: | MicroRNAs (miRNAs) are short non-coding RNAs of 21–23 nucleotides that play important roles in virtually all biological pathways in mammals and in other multicellular organisms. miR-23a and miR-23b (miR-23a/b) are critical oncomiRs (miRNAs that are associated with human cancers) of gastric cancer, but their detailed roles in the initiation and progression of gastric cancer remain to be elucidated. In this study, we found that miR-23a/b were consistently upregulated in gastric cancer tissues. We then investigated the molecular mechanisms through which miR-23a/b contribute to gastric cancer and identified programmed cell death 4 (PDCD4) as a direct target gene of miR-23a/b. In contrast to the upregulated expression levels of miR-23a/b, PDCD4 protein levels were dramatically downregulated and inversely correlated with miR-23a/b in gastric cancer tissues. Moreover, we observed that cell apoptosis was increased by miR-23a/b inhibitors and decreased by miR-23a/b mimics in gastric cancer cells and that the restoration of PDCD4 expression attenuated the anti-apoptotic effects of miR-23a/b in gastric cancer cells, indicating that PDCD4 is a direct mediator of miR-23a/b functions. Finally, we showed that miR-23a/b significantly suppressed PDCD4 expression and enhanced tumor growth in a gastric cancer xenograft mouse model. Taken together, this study highlights an important role for miR-23a/b as oncomiRs in gastric cancer through the inhibition of PDCD4 translation. These findings may shed new light on the molecular mechanism of gastric carcinogenesis and provide a new avenue for gastric cancer treatment. |
| Databáze: | OpenAIRE |
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