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

ABSTRACT: 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.

SUBMITTER: Tilija Pun N

PROVIDER: S-EPMC6275284 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Tilija Pun Nirmala N Khakurel Amrita A Shrestha Aastha A Kim Sang-Hyun SH Park Pil-Hoon PH

FEBS open bio 20181112 12

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 elem ...[more]

PMID: 30524947

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Project description:The yeast M-NM-6-crystallin Zta1p interacts specifically with RNA sequences rich in adenine and uracil (AU-rich element). We have looked for possible targets of Zta1p through a comparative transcriptional analysis of the yeast defective in ZTA1 (M-NM-^Tzta1) versus the wild-type by microarray. This revealed that a group of genes implicated on amino acid biosynthesis are affected by the lack of ZTA1. The effect on one of the targets ARG4 was studied in more detail, revealing a clear positive correlation between ZTA1 and ARG4 expression at the mRNA level. We demonstrate that Zta1p is able to bind specifically to the 3M-bM-^@M-^YUTR AU-rich elements of ARG4 mRNA in vitro, suggesting that the mechanism by which ZTA1 modulates the expression of ARG4 is probably mediated by this mRNA binding ability. Moreover, the expression of ZTA1 is also under the control of the TOR pathway, and under Gcn4p, which regulates genes implicated in the response to nutrient availability and the general amino acid control (GAAC). In summary, our results shed light on the functional role of the M-NM-6-crystallin family as stress response proteins, with a conserved functional role, from yeast to humans, in the post-transcriptional regulation of genes that need to be rapidly activated for cell defense. Triplicate biological replicate experiments were performed, where the two strains, M-bM-^HM-^Fzta1 and wild-type, were grown in the presence or absence of hydrogen peroxide. The experimental design was defined to directly compare the M-bM-^HM-^Fzta1 versus the wild-type strain in either of the two hydrogen peroxide treatment conditions (i.e. treated M-bM-^HM-^Fzta1 versus treated wt, or untreated M-bM-^HM-^Fzta1 versus untreated wt). A duplicate hybridization on a separate array with dye swapping was performed in each case to correct for dye bias effects. Thus, a total of 12 array data sets were produced as a result of processing three experimental pairs of samples, for each of two treatment conditions, with dye swap duplicates.

Dataset Information

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

Publications

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

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