TGF-β1-induced miR-202 mediates drug resistance by inhibiting apoptosis in human osteosarcoma.
OBJECTIVE
A number of studies have demonstrated that microRNAs play a critical role in osteosarcoma progression, therapy and drug resistance. MicroRNA-202 has proven to be dysregulated in many human cancer studies. This study aimed to explore miR-202 contributions to drug resistance in osteosarcoma.


METHODS
miR-202 expression was measured by real-time PCR in patient tissues, cell lines or cells treated with TGF-β1, using siRNA to knock down the expression of Smad2, Smad3 and Smad4. miR-202 mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to observe effects on cell apoptosis and drug resistance. Moreover, relationships of miR-202 level with PDCD4 were investigated by luciferase reporter assay, real-time PCR and Western blotting.


RESULTS
We found that miR-202 is overexpressed in osteosarcoma tissues when compared with normal human osteoblasts and TGF-β1 can induce the expression of miR-202. Transfection of miR-202 mimics into osteosarcoma cell lines significantly promotes chemotherapy resistance by targeting PDCD4, a tumor suppressor which is involved in apoptosis. In contrast, transfection of miR-202 inhibitor enhances the drug sensitivity and apoptosis.


CONCLUSIONS
This study provides new insights into miRNA-202 in osteosarcoma as a potential molecular target for chemotherapy.
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Zaijun
Z
Lin
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Dianwen
D
Song
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Haifeng
H
Wei
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Xinghai
X
Yang
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Tielong
T
Liu
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Wangjun
W
Yan
Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. jianru365@163.com.
Jianru
J
Xiao
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; C569392:MIRN202 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053773:Transforming Growth Factor beta1
Drug resistance; Osteosarcoma; PDCD4; miR-202