MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN

BMC Cancer

Research Article

Zhang Qing-yu¹  Fu Yan-chao¹  Han Lei²  Wang Guang-xiu²  Pu Pei-yu²  Jia Zhi-fan²  Zhang An-ling²  Yue Xiao²  Kang Chun-sheng²  Zhang Chun-zhi³ 

[1] Department of Gastroenterology, Tianjin Medical University General Hospital, 300052, Tianjin, China;Department of Neurosurgery, Tianjin Medical University General Hospital and Lab of Neuro-oncology, Tianjin Neurological Institute, 300052, Tianjin, China;Department of Neurosurgery, Tianjin Medical University General Hospital and Lab of Neuro-oncology, Tianjin Neurological Institute, 300052, Tianjin, China;Department of Radiation Oncology, Tianjin Huan Hu Hospital, 300060, Tianjin, China;

关键词: Gastric Cancer;    Gastric Cancer Cell;    Luciferase Reporter Assay;    SGC7901 Cell;    PTEN Expression;   

DOI  :  10.1186/1471-2407-10-367

 received in 2010-01-06, accepted in 2010-07-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) can function as either oncogenes or tumor suppressor genes via regulation of cell proliferation and/or apoptosis. MiR-221 and miR-222 were discovered to induce cell growth and cell cycle progression via direct targeting of p27 and p57 in various human malignancies. However, the roles of miR-221 and miR-222 have not been reported in human gastric cancer. In this study, we examined the impact of miR-221 and miR-222 on human gastric cancer cells, and identified target genes for miR-221 and miR-222 that might mediate their biology.MethodsThe human gastric cancer cell line SGC7901 was transfected with AS-miR-221/222 or transduced with pMSCV-miR-221/222 to knockdown or restore expression of miR-221 and miR-222, respectively. The effects of miR-221 and miR-222 were then assessed by cell viability, cell cycle analysis, apoptosis, transwell, and clonogenic assay. Potential target genes were identified by Western blot and luciferase reporter assay.ResultsUpregulation of miR-221 and miR-222 induced the malignant phenotype of SGC7901 cells, whereas knockdown of miR-221 and miR-222 reversed this phenotype via induction of PTEN expression. In addition, knockdonwn of miR-221 and miR-222 inhibited cell growth and invasion and increased the radiosensitivity of SGC7901 cells. Notably, the seed sequence of miR-221 and miR-222 matched the 3'UTR of PTEN, and introducing a PTEN cDNA without the 3'UTR into SGC7901 cells abrogated the miR-221 and miR-222-induced malignant phenotype. PTEN-3'UTR luciferase reporter assay confirmed PTEN as a direct target of miR-221 and miR-222.ConclusionThese results demonstrate that miR-221 and miR-222 regulate radiosensitivity, and cell growth and invasion of SGC7901 cells, possibly via direct modulation of PTEN expression. Our study suggests that inhibition of miR-221 and miR-222 might form a novel therapeutic strategy for human gastric cancer.

【 授权许可】

Unknown   
© Chun-zhi et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.