PUMA is a novel target of miR-221/222 in human epithelial cancers.
miR-221 and miR-222 (miR-221/222) are frequently up-regulated in human epithelial cancers. However, the mechanism of miR-221/222 action involved in carcinogenesis has not been extensively studied. Here, we found that reduction of miR-221/222 inhibited cell proliferation and induced mitochondrial-mediated apoptosis in human epithelial cancer cells (A549 lung cancer and MCF-7 breast cancer cells). Bioinformatics and luciferase reporter assays showed that miR-221/222 co-modulated the p53 upregulated modulator of apoptosis (PUMA) expression by directly targeting the binding site within the 3'UTR. Together, these findings suggest that PUMA is a direct target of miR-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers.
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, PR China.
Chunzhi
C
Zhang
Junxia
J
Zhang
Anlin
A
Zhang
Yingyi
Y
Wang
Lei
L
Han
Yongping
Y
You
Peiyu
P
Pu
Chunsheng
C
Kang
D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C438378:BBC3 protein, human; C525709:MIR221, human; C525710:MIR222, human