MicroRNA-221 targeting PI3-K/Akt signaling axis induces cell proliferation and BCNU resistance in human glioblastoma.
MicroRNAs (miRNAs) are short regulatory RNAs that negatively regulate protein biosynthesis at the post-transcriptional level and participate in the pathogenesis of different types of human cancers, including glioblastoma. In particular, the levels of miRNA-221 are overexpressed in many cancers and miRNA-221 exerts its functions as an oncogene. Nevertheless, the roles of miRNA-221 in carmustine (BCNU)-resistant glioma cells have not been totally elucidated. In the present study, we explored the effects of miRNA-221 on BCNU-resistant glioma cells and the possible molecular mechanisms by which miRNA-221 mediated the cell proliferation, survival, apoptosis and BCNU resistance were investigated. We found that miR-221 was overexpressed in glioma cells, including BCNU-resistant cells. Moreover, we found that miR-221 regulated cell proliferation and BCNU resistance in glioma cells. Overexpression of miR-221 led to cell survival and BCNU resistance and reduced cell apoptosis induced by BCNU, whereas knockdown of miR-221 inhibited cell proliferation and prompted BCNU sensitivity and cell apoptosis. Further investigation revealed that miR-221 down-regulated PTEN and activated Akt, which resulted in cell survival and BCNU resistance. Overexpression of PTEN lacking 3'UTR or PI3-K/Akt specific inhibitor wortmannin attenuated miR-221-mediated BCNU resistance and prompted cell apoptosis. We propose that miR-221 regulated cell proliferation and BCNU resistance in glioma cells by targeting PI3-K/PTEN/Akt signaling axis. Our findings may provide a new potential therapeutic target for treatment of glioblastoma.
Department of Oncology, Armed Police Corps Hospital, Guangzhou, China; Department of Pathology, School of Medicine, Jinan University, Guangzhou, China.
Qiang
Q
Xie
Yongrong
Y
Yan
Zuoping
Z
Huang
Xueyun
X
Zhong
Lei
L
Huang
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D002330:Carmustine / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
D018906:Antineoplastic Agents, Alkylating; D002330:Carmustine; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C525709:MIR221, human; C494929:PTEN protein, human
Akt; BCNU; PTEN; glioma; miR-221