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Mutual inhibitions between epidermal growth factor receptor signaling and miR‐124a control pancreatic progenitor proliferation
Author(s) -
Zhang Zhenwu,
Zhai Wenjun,
Liang Jie,
Chen Zhenbao,
Ma Mingjun,
Zhao Yicheng,
Liang Yang,
Li Xuyan,
Teng ChunBo
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27967
Subject(s) - protein kinase b , microbiology and biotechnology , stat3 , janus kinase , epidermal growth factor , epidermal growth factor receptor , mapk/erk pathway , cancer research , pi3k/akt/mtor pathway , progenitor cell , signal transduction , biology , chemistry , stem cell , receptor , biochemistry
Pancreatic stem/progenitor cells convert from a proliferative to a differentiated fate passing through proliferation cease to a resting state. However, the molecular mechanisms of cell cycle arrest are poorly understood. In this study, we demonstrated that the microRNA‐124a (miR‐124a) inhibited the proliferation of pancreatic progenitor cells both in vitro and ex vivo and promoted a quiescent state. The miR‐124a directly targeted SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1), IQ motif‐containing GTPase‐activating protein 1 (IQGAP1), signal transducer and activator of transcription 3 (STAT3), and cyclin D2 (CCND2), thereby inactivating epidermal growth factor receptor (EGFR) downstream signaling pathways including mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MEK/ERK), phosphatidylinositol 3‐kinase‐protein kinase B (PI3K/AKT) and Janus kinase (JAK)/STAT3. miR‐124a blocked cell proliferation mainly through targeting STAT3 to inhibit PI3K/AKT and JAK/STAT3 signaling. Moreover, miR‐124a expression was negatively regulated by EGFR downstream PI3K/AKT signaling. These results indicated that miR‐124a and EGFR signaling mutually interact to form a regulating circuit that determines the proliferation of pancreatic progenitor cells.