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Identification of microRNAs regulating Hlxb9 gene expression during the induction of insulin‐producing cells
Author(s) -
Mu Changzheng,
Wang Tao,
Wang Xiaomei,
Tian He,
Liu Yong
Publication year - 2016
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10586
Subject(s) - pdx1 , microrna , pax4 , biology , transcription factor , microbiology and biotechnology , gene expression , cellular differentiation , progenitor cell , cancer research , homeobox , stem cell , gene , genetics
Abstract Bone marrow mesenchymal stem cells (bMSCs) with the capacity of self‐ renewal and multilineage differentiation are promising sources for cell replacement therapy in diabetes. Here, we developed an effective method with activin A, conophylline, and nicotinamide to induce mouse bMSCs to differentiate into insulin‐producing cells (IPCs). The homeobox gene Hlxb9 (encoding HB9) is prominently expressed in adult human pancreas, which can also play a key role during the induction of IPCs. To find the microRNAs (miRNAs) regulating Hlxb9 gene expression, we respectively used miRanda and TargetScan to predict and got the intersection, miR‐200a and miR‐141, further identified by the Dual‐Luciferase assay. The results illustrated miR‐200a and miR‐141 could inhibit the expression of Hlxb9 by binding to its mRNA 3′UTR. Furthermore, the expression of miR‐200a and miR‐141 was almost reciprocal to that of Hlxb9. Overexpression of miR‐200a and miR‐141 downregulated the expression of pancreatic progenitor cell markers Hlxb9 and Pdx1. Therefore, miR‐200a and miR‐141 may directly or indirectly regulate the expression of pancreatic islet transcription factors to control the differentiation of IPCs.