MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1.
The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention.
Department of Hematology, The Second Affiliated Hospital οf Xi'an Jiaotong University, Xi'an, Shaanxi 710005, P.R. China.
Lu
L
Qian
Department of Hematology, The Second Affiliated Hospital οf Xi'an Jiaotong University, Xi'an, Shaanxi 710005, P.R. China.
Wanggang
W
Zhang
Department of Hematology, The Second Affiliated Hospital οf Xi'an Jiaotong University, Xi'an, Shaanxi 710005, P.R. China.
Bo
B
Lei
Department of Hematology, The Second Affiliated Hospital οf Xi'an Jiaotong University, Xi'an, Shaanxi 710005, P.R. China.
Aili
A
He
Department of Gynaecology and Obstetrics, Xi'an No. 4 Hospital, Xi'an, Shaanxi 710004, P.R. China.
Lianhong
L
Ye
Department of Surgery, Xi'an No. 4 Hospital, Xi'an, Shaanxi 710004, P.R. China.
Xingzhou
X
Li
Department of Internal Medicine, Xi'an No. 4 Hospital, Xi'an, Shaanxi 710004, P.R. China.
Xin
X
Dong
D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D064368:Healthy Volunteers; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D051881:Receptor, Notch1 / Q000097:blood / Q000235:genetics*
D014408:Biomarkers, Tumor; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1
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