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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Main Authors: Nirmala Tilija Pun, Amrita Khakurel, Aastha Shrestha, Sang‐Hyun Kim, Pil‐Hoon Park
Format: Article
Language:English
Published: Wiley 2018-12-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.12541
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author Nirmala Tilija Pun
Amrita Khakurel
Aastha Shrestha
Sang‐Hyun Kim
Pil‐Hoon Park
author_facet Nirmala Tilija Pun
Amrita Khakurel
Aastha Shrestha
Sang‐Hyun Kim
Pil‐Hoon Park
author_sort Nirmala Tilija Pun
collection DOAJ
description 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.
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spelling doaj.art-5eae0806083b45668ef5b9336798c0fa2023-03-14T13:06:01ZengWileyFEBS Open Bio2211-54632018-12-018121964197610.1002/2211-5463.12541Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectinNirmala Tilija Pun0Amrita Khakurel1Aastha Shrestha2Sang‐Hyun Kim3Pil‐Hoon Park4College of Pharmacy Yeungnam University Gyeongsan KoreaCollege of Pharmacy Yeungnam University Gyeongsan KoreaCollege of Pharmacy Yeungnam University Gyeongsan KoreaDepartment of Pharmacology School of Medicine Kyungpook National University Daegu KoreaCollege of Pharmacy Yeungnam University Gyeongsan KoreaAdiponectin 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.https://doi.org/10.1002/2211-5463.12541adiponectinAUF1Bcl‐2hepatic cancerTTP
spellingShingle Nirmala Tilija Pun
Amrita Khakurel
Aastha Shrestha
Sang‐Hyun Kim
Pil‐Hoon Park
Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin
FEBS Open Bio
adiponectin
AUF1
Bcl‐2
hepatic cancer
TTP
title Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin
title_full Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin
title_fullStr Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin
title_full_unstemmed Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin
title_short Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin
title_sort critical role of tristetraprolin and au rich element rna binding protein 1 in the suppression of cancer cell growth by globular adiponectin
topic adiponectin
AUF1
Bcl‐2
hepatic cancer
TTP
url https://doi.org/10.1002/2211-5463.12541
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