Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin

Adiponectin exhibits potent antitumor activities. Herein, we examined the molecular mechanisms underlying suppression of tumor growth by globular adiponectin (gAcrp). We demonstrated that gAcrp suppressed B‐cell lymphoma 2 (Bcl‐2) expression, an anti‐apoptotic gene, by inducing its mRNA destabilizat...

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Bibliographic Details
Published in:FEBS open bio 2018-12, Vol.8 (12), p.1964-1976
Main Authors: Tilija Pun, Nirmala, Khakurel, Amrita, Shrestha, Aastha, Kim, Sang‐Hyun, Park, Pil‐Hoon
Format: Article
Language:English
Subjects:
Adiponectin
Antitumor activity
Apoptosis
AUF1
Bcl‐2
Breast cancer
Cancer
Caspase
Cell culture
Cell cycle
Cell growth
Cell viability
Dehydrogenases
Genes
hepatic cancer
Kinases
Liver
Liver cancer
Lymphoma
Membranes
Molecular modelling
mRNA stability
Polymerase chain reaction
Proteins
Regulatory proteins
RNA-binding protein
TTP
Variance analysis
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Summary:Adiponectin exhibits potent antitumor activities. Herein, we examined the molecular mechanisms underlying suppression of tumor growth by globular adiponectin (gAcrp). We demonstrated that gAcrp suppressed B‐cell lymphoma 2 (Bcl‐2) expression, an anti‐apoptotic gene, by inducing its mRNA destabilization, which was accompanied with a decrease in cell viability and increased caspase‐3 activity in hepatic cancer cells. In addition, gAcrp increased expression of tristetraprolin (TTP) and AU‐rich element RNA‐binding protein 1 (AUF1), which are mRNA stability regulatory proteins. Moreover, gAcrp‐induced suppression of Bcl‐2 expression was abrogated by knockdown of TTP or AUF1. These data indicate that gAcrp induces apoptosis of hepatic cancer cells by TTP‐ and AUF1‐mediated Bcl‐2 mRNA destabilization, and further suggest that TTP and AUF1 are novel targets mediating the antitumor activity of adiponectin. Globular adiponectin (gAcrp) increases tristetraprolin (TTP) and AU‐rich element RNA‐binding protein 1 (AUF1) expression in hepatic cancer cells. TTP and AUF1 bind to B‐cell lymphoma 2 (Bcl‐2) mRNA and induce destabilization, which leads to the suppression of Bcl‐2 expression, induction of apoptosis, and finally inhibition of tumor growth. The molecular mechanisms by which gAcrp induces expression of AUF1 and TTP remain to be determined.
ISSN:2211-5463
2211-5463
DOI:10.1002/2211-5463.12541