Adenylate cyclase 7 regulated by miR-192 promotes ATRA-induced differentiation of acute promyelocytic leukemia cells

Adenylate cyclase 7 (AC7) has been reported to participate in various biological processes during cancer progression. However, the roles of AC7 in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells are still unknown. In this study, firstly, our results...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2018-11, Vol.506 (3), p.543-547
Main Authors: He, Bing, Chang, Yanyan, Yang, Chao, Zhang, Zhanglin, Xu, Guiping, Feng, Xianqi, Zhuang, Likun
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
AC7
Adenylyl Cyclases - genetics
Adenylyl Cyclases - metabolism
AMP
APL
ATRA
Base Sequence
BIOLOGICAL MARKERS
cAMP
CELL DIFFERENTIATION
Cell Differentiation - drug effects
Cell Line, Tumor
CYCLASES
Cyclic AMP - biosynthesis
Down-Regulation - drug effects
Down-Regulation - genetics
Gene Expression Regulation, Leukemic - drug effects
Gene Knockdown Techniques
Humans
LEUKEMIA
Leukemia, Promyelocytic, Acute - diagnosis
Leukemia, Promyelocytic, Acute - genetics
Leukemia, Promyelocytic, Acute - pathology
MESSENGER-RNA
MicroRNAs - genetics
MicroRNAs - metabolism
miR-192
Recurrence
RETINOIC ACID
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tretinoin - pharmacology
Up-Regulation - drug effects
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Summary:Adenylate cyclase 7 (AC7) has been reported to participate in various biological processes during cancer progression. However, the roles of AC7 in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells are still unknown. In this study, firstly, our results showed that AC7 affected intracellular cAMP level and influenced ATRA-induced differentiation of APL cells. Secondly, we revealed that miR-192 could directly target AC7 expression and knockdown of miR-192 promoted ATRA-induced APL cell differentiation by regulating AC7 expression. Furthermore, we found that AC7 expression was lower in patients with relapsed APL than that in patients with newly diagnosed APL, while miR-192 expression was relatively higher in patients with relapsed APL. Taken together, our results show that miR-192-mediated AC7 could play important roles in differentiation of APL cells, AC7 and miR-192 might be new biomarkers and therapeutic targets for patients with relapsed APL. •AC7 affects cAMP production in APL cells.•Knockdown of AC7 inhibits ATRA-induced differentiation of APL cells.•MiR-192 directly targets 3′ UTR of AC7 mRNA and inhibits its expression.•MiR-192 knockdown promotes ATRA-induced differentiation of APL cells by up-regulating AC7.•AC7 and miR-192 expression levels are associated with the relapse of APL patients.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.10.125