MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN
Open Access
- 12 July 2010
- journal article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 10 (1), 367
- https://doi.org/10.1186/1471-2407-10-367
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
This publication has 58 references indexed in Scilit:
- RETRACTED: miR-221&222 Regulate TRAIL Resistance and Enhance Tumorigenicity through PTEN and TIMP3 DownregulationCancer Cell, 2009
- Argonaute HITS-CLIP decodes microRNA–mRNA interaction mapsNature, 2009
- Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinomaBMC Cancer, 2009
- Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cellsNucleic Acids Research, 2009
- Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancerNucleic Acids Research, 2009
- A single anti-microRNA antisense oligodeoxyribonucleotide (AMO) targeting multiple microRNAs offers an improved approach for microRNA interferenceNucleic Acids Research, 2009
- The radiosensitization effect of parthenolide in prostate cancer cells is mediated by nuclear factor-κB inhibition and enhanced by the presence of PTENMolecular Cancer Therapeutics, 2007
- MicroRNA Signatures in Human CancersNature Reviews Cancer, 2006
- Akt phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancerInternational Journal of Cancer, 2005
- MicroRNA Gene Expression Deregulation in Human Breast CancerCancer Research, 2005