ADCY7 supports development of acute myeloid leukemia

Chunling Li; Jingjing Xie; Zhigang Lu; Chen Chen; Yancun Yin; Renhui Zhan; Yi Fang; Xuemei Hu; Cheng Cheng Zhang

doi:10.1016/j.bbrc.2015.07.123

ADCY7 supports development of acute myeloid leukemia

Biochem Biophys Res Commun. 2015 Sep 11;465(1):47-52. doi: 10.1016/j.bbrc.2015.07.123. Epub 2015 Jul 26.

Authors

Chunling Li¹, Jingjing Xie², Zhigang Lu³, Chen Chen¹, Yancun Yin¹, Renhui Zhan¹, Yi Fang³, Xuemei Hu¹, Cheng Cheng Zhang⁴

Affiliations

¹ Taishan Scholar Immunology Program, Binzhou Medical University, Yantai, Shandong 264003, China.
² Taishan Scholar Immunology Program, Binzhou Medical University, Yantai, Shandong 264003, China; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
³ Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁴ Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: [email protected].

Abstract

Acute myeloid leukemia (AML) is the most common adult acute leukemia. Despite treatment, the majority of the AML patients relapse within 5 years. In silico analysis of several available databases of AML patients showed that the expression of adenylate cyclase 7 (ADCY7) significantly inversely correlates with the overall survival of AML patients. To determine whether ADCY7 supports AML development, we employed an shRNA-encoding lentivirus system to inhibit adcy7 expression in human AML cells including U937, MV4-11, and THP-1 cells. The ADCY7 deficiency resulted in decreased cell growth, elevated apoptosis, and lower c-Myc expression of these leukemia cells. This indicates that G protein-coupled receptor signaling contributes to AML pathogenesis. Our study suggests that inhibition of ADCY7 may be novel strategy for treating leukemia.

Keywords: ADCY7; Acute myeloid leukemia; Apoptosis; Cell growth; G protein-coupled receptor; shRNA.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenylyl Cyclases / genetics*
Adenylyl Cyclases / metabolism
Apoptosis / genetics
Cell Cycle / genetics
Cell Line, Tumor
Cell Proliferation
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism
Gene Expression Regulation, Leukemic*
Genetic Vectors
Humans
Lentivirus / genetics
Leukemia, Myeloid, Acute / classification
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / mortality
Leukemia, Myeloid, Acute / pathology
Proto-Oncogene Proteins c-myc / antagonists & inhibitors
Proto-Oncogene Proteins c-myc / genetics*
Proto-Oncogene Proteins c-myc / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism
Signal Transduction
Survival Analysis

Substances

ADGRG1 protein, human
CCDC6 protein, human
Cytoskeletal Proteins
Proto-Oncogene Proteins c-myc
RNA, Small Interfering
Receptors, G-Protein-Coupled
Adenylyl Cyclases
adenylyl cyclase 7

Abstract

Publication types

MeSH terms

Substances

Grants and funding