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

Authors: Chun-Zhi Z; Lei H; An-Ling Z; Yan-Chao F; Xiao Y; Guang-Xiu W; Zhi-Fan J; Pei-Yu P; Qing-Yu Z; Chun-Sheng K

Abstract: BACKGROUND: MicroRNAs (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. METHODS: The 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. RESULTS: Upregulation 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. CONCLUSION: These 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.

Keywords: Animals; Apoptosis; Blotting, Northern; Blotting, Western; Cell Adhesion; Cell Cycle; Cell Movement; *Cell Proliferation; Cells, Cultured; Fibroblasts/cytology/metabolism; Gamma Rays; *Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Kidney/cytology/metabolism; Mice; MicroRNAs/*physiology; NIH 3T3 Cells; PTEN Phosphohydrolase/antagonists & inhibitors/genetics/*metabolism; RNA, Messenger/genetics; Radiation Tolerance/*genetics; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms/genetics/*pathology/radiotherapy
Journal: BMC cancer
Volume: 10
Pages: 367
Date: July 14, 2010
PMID: 20618998
Select reference article to upload


Citation:

Chun-Zhi Z, Lei H, An-Ling Z, Yan-Chao F, Xiao Y, Guang-Xiu W, Zhi-Fan J, Pei-Yu P, Qing-Yu Z, Chun-Sheng K (2010) MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN. BMC cancer 10: 367.


Lifespan Factors:
  • miR222 microRNA 222
  • miR221 microRNA 221


  • Update (Admin) | Auto-Update

    Comment on This Data Unit