Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation

Yikai Zhang; Chengwu Zeng; Shuai Lu; Tianyu Qin; Lijian Yang; Shaohua Chen; Jie Chen; Yangqiu Li

doi:10.1016/j.bbrc.2016.09.020

Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation

Biochem Biophys Res Commun. 2016 Sep 30;478(4):1758-63. doi: 10.1016/j.bbrc.2016.09.020. Epub 2016 Sep 6.

Authors

Yikai Zhang¹, Chengwu Zeng², Shuai Lu³, Tianyu Qin⁴, Lijian Yang⁴, Shaohua Chen⁴, Jie Chen⁵, Yangqiu Li⁶

Affiliations

¹ 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.
² 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.
³ Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China.
⁴ Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China.
⁵ First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
⁶ 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.

PMID: 27613090
DOI: 10.1016/j.bbrc.2016.09.020

Abstract

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.

Keywords: 3′-untranslated regions; Acute promyelocytic leukemia; MicroRNAs; PML-RARα; Proliferation; Small non-coding RNAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Blotting, Western
Cell Line, Tumor
Cell Proliferation / genetics*
Female
Gene Expression Regulation, Leukemic*
Humans
Immediate-Early Proteins / genetics
Leukemia, Promyelocytic, Acute / genetics*
Leukemia, Promyelocytic, Acute / metabolism
Leukemia, Promyelocytic, Acute / pathology
MAP Kinase Kinase Kinases / genetics
MAP Kinase Signaling System / genetics
Male
MicroRNAs / genetics*
Middle Aged
Mitogen-Activated Protein Kinase Kinase Kinase 11
Phosphatidylinositol 3-Kinases / metabolism
Positive Regulatory Domain I-Binding Factor 1
Repressor Proteins / genetics
Reverse Transcriptase Polymerase Chain Reaction
Ribosomal Protein S6 Kinases, 90-kDa / genetics
Tumor Suppressor Proteins / genetics
Young Adult

Substances

Immediate-Early Proteins
MIRN125 microRNA, human
MicroRNAs
Repressor Proteins
Tumor Suppressor Proteins
PRDM1 protein, human
BTG2 protein, human
Positive Regulatory Domain I-Binding Factor 1
Phosphatidylinositol 3-Kinases
RPS6KA1 protein, human
Ribosomal Protein S6 Kinases, 90-kDa
MAP Kinase Kinase Kinases