Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation.
Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RARα fusion protein. We have previously found that PML-RARα-regulated miR-125b is highly expressed in APL; however, the characteristics of the regulatory effects and mechanisms of miR-125b involved in APL proliferation have yet to be clarified. In this study, we demonstrate that miR-125b promotes the proliferation of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways. Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets of miR-125b, which we verified using luciferase reporter constructs. Moreover, we demonstrate that the expression of miR-125b targets is downregulated in leukemic cells in patients with APL. Thus, our results provide evidence that miR-125b can modulate multiple oncogenic cell proliferation pathways and may be a novel therapeutic target for APL.
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China; First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
Yikai
Y
Zhang
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China; First Affiliated Hospital, Jinan University, Guangzhou 510632, China. Electronic address: bio-zcw@163.com.
Chengwu
C
Zeng
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China.
Shuai
S
Lu
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China.
Tianyu
T
Qin
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China.
Lijian
L
Yang
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China.
Shaohua
S
Chen
First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
Jie
J
Chen
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China; First Affiliated Hospital, Jinan University, Guangzhou 510632, China. Electronic address: yangqiuli@hotmail.com.
Yangqiu
Y
Li
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
D017874:Immediate-Early Proteins; D020930:MAP Kinase Kinase Kinases; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D025521:Tumor Suppressor Proteins; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C531888:MIRN125 microRNA, human; C087042:PRDM1 protein, human; C070114:BTG2 protein, human; C069329:RPS6KA1 protein, human
3′-untranslated regions; Acute promyelocytic leukemia; MicroRNAs; PML-RARα; Proliferation; Small non-coding RNAs