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

Biochem Biophys Res Commun. 2018 Nov 30;506(3):543-547. doi: 10.1016/j.bbrc.2018.10.125. Epub 2018 Oct 23.

Abstract

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.

Keywords: AC7; APL; ATRA; Cell differentiation; cAMP; miR-192.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Base Sequence
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cyclic AMP / biosynthesis
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Gene Expression Regulation, Leukemic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Leukemia, Promyelocytic, Acute / diagnosis
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recurrence
  • Tretinoin / pharmacology*
  • Up-Regulation / drug effects

Substances

  • MIRN192 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Tretinoin
  • Cyclic AMP
  • Adenylyl Cyclases
  • adenylyl cyclase 7