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MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma.
PLoS One. 2013; 8(1):e53906.Plos

Abstract

BACKGROUND

MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. Specifically, microRNA-221 (miR-221) is overexpressed in many human cancers, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-221 in human osteosarcoma has not been totally elucidated. In the present study, the effects of miR-221 on osteosarcoma and the possible mechanism by which miR-221 affected the survival, apoptosis, and cisplatin resistance of osteosarcoma were investigated.

METHODOLOGY/PRINCIPAL FINDINGS

Real-time quantitative PCR analysis revealed miR-221 was significantly upregulated in osteosarcoma cell lines than in osteoblasts. Both human osteosarcoma cell lines SOSP-9607 and MG63 were transfected with miR-221 mimic or inhibitor to regulate miR-221 expression. The effects of miR-221 were then assessed by cell viability, cell cycle analysis, apoptosis assay, and cisplatin resistance assay. In both cells, upregulation of miR-221 induced cell survival and cisplatin resistance and reduced cell apoptosis. In addition, knockdown of miR-221 inhibited cell growth and cisplatin resistance and induced cell apoptosis. Potential target genes of miR-221 were predicted using bioinformatics. Moreover, luciferase reporter assay and western blot confirmed that PTEN was a direct target of miR-221. Furthermore, introduction of PTEN cDNA lacking 3'-UTR or PI3K inhibitor LY294002 abrogated miR-221-induced cisplatin resistance. Finally, both miR-221 and PTEN expression levels in osteosarcoma samples were examined by using real-time quantitative PCR and immunohistochemistry. High miR-221 expression level and inverse correlation between miR-221 and PTEN levels were revealed in osteosarcoma tissues.

CONCLUSIONS/SIGNIFICANCE

These results for the first time demonstrate that upregulation of miR-221 induces the malignant phenotype of human osteosarcoma whereas knockdown of miR-221 reverses this phenotype, suggesting that miR-221 could be a potential target for osteosarcoma treatment.

Authors+Show Affiliations

Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23372675

Citation

Zhao, Guangyi, et al. "MicroRNA-221 Induces Cell Survival and Cisplatin Resistance Through PI3K/Akt Pathway in Human Osteosarcoma." PloS One, vol. 8, no. 1, 2013, pp. e53906.
Zhao G, Cai C, Yang T, et al. MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS ONE. 2013;8(1):e53906.
Zhao, G., Cai, C., Yang, T., Qiu, X., Liao, B., Li, W., Ji, Z., Zhao, J., Zhao, H., Guo, M., Ma, Q., Xiao, C., Fan, Q., & Ma, B. (2013). MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PloS One, 8(1), e53906. https://doi.org/10.1371/journal.pone.0053906
Zhao G, et al. MicroRNA-221 Induces Cell Survival and Cisplatin Resistance Through PI3K/Akt Pathway in Human Osteosarcoma. PLoS ONE. 2013;8(1):e53906. PubMed PMID: 23372675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. AU - Zhao,Guangyi, AU - Cai,Chengkui, AU - Yang,Tongtao, AU - Qiu,Xiuchun, AU - Liao,Bo, AU - Li,Wei, AU - Ji,Zhenwei, AU - Zhao,Jian, AU - Zhao,Haien, AU - Guo,Mingjun, AU - Ma,Qiong, AU - Xiao,Chun, AU - Fan,Qingyu, AU - Ma,Baoan, Y1 - 2013/01/23/ PY - 2012/08/06/received PY - 2012/12/04/accepted PY - 2013/2/2/entrez PY - 2013/2/2/pubmed PY - 2013/7/23/medline SP - e53906 EP - e53906 JF - PloS one JO - PLoS ONE VL - 8 IS - 1 N2 - BACKGROUND: MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. Specifically, microRNA-221 (miR-221) is overexpressed in many human cancers, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-221 in human osteosarcoma has not been totally elucidated. In the present study, the effects of miR-221 on osteosarcoma and the possible mechanism by which miR-221 affected the survival, apoptosis, and cisplatin resistance of osteosarcoma were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Real-time quantitative PCR analysis revealed miR-221 was significantly upregulated in osteosarcoma cell lines than in osteoblasts. Both human osteosarcoma cell lines SOSP-9607 and MG63 were transfected with miR-221 mimic or inhibitor to regulate miR-221 expression. The effects of miR-221 were then assessed by cell viability, cell cycle analysis, apoptosis assay, and cisplatin resistance assay. In both cells, upregulation of miR-221 induced cell survival and cisplatin resistance and reduced cell apoptosis. In addition, knockdown of miR-221 inhibited cell growth and cisplatin resistance and induced cell apoptosis. Potential target genes of miR-221 were predicted using bioinformatics. Moreover, luciferase reporter assay and western blot confirmed that PTEN was a direct target of miR-221. Furthermore, introduction of PTEN cDNA lacking 3'-UTR or PI3K inhibitor LY294002 abrogated miR-221-induced cisplatin resistance. Finally, both miR-221 and PTEN expression levels in osteosarcoma samples were examined by using real-time quantitative PCR and immunohistochemistry. High miR-221 expression level and inverse correlation between miR-221 and PTEN levels were revealed in osteosarcoma tissues. CONCLUSIONS/SIGNIFICANCE: These results for the first time demonstrate that upregulation of miR-221 induces the malignant phenotype of human osteosarcoma whereas knockdown of miR-221 reverses this phenotype, suggesting that miR-221 could be a potential target for osteosarcoma treatment. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23372675/MicroRNA_221_induces_cell_survival_and_cisplatin_resistance_through_PI3K/Akt_pathway_in_human_osteosarcoma_ L2 - http://dx.plos.org/10.1371/journal.pone.0053906 DB - PRIME DP - Unbound Medicine ER -