Dataset Information

FATS regulates polyamine biosynthesis by promoting ODC degradation in an ER?-dependent manner in non-small-cell lung cancer.

ABSTRACT: Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be significantly downregulated in NSCLC tissues compared with paired adjacent normal tissues and was associated with the survival of NSCLC patients. We further showed that the presence of the tumour suppressor FATS in NSCLC cells led to apoptosis by inducing pro-death autophagy. In addition, FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, which was partially dependent on oestrogen receptor (ER). Furthermore, FATS was observed to bind to ER? and translocate to the cytosol, leading to ODC degradation. The findings of our study demonstrate that FATS plays important roles in polyamine metabolism in NSCLC and provides a new perspective for NSCLC progression.

SUBMITTER: Qiu L

PROVIDER: S-EPMC7547721 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer.

Qiu Li L Hu Linfei L Wang Huijuan H Li Jinling J Ruan Xianhui X Sun Bingsheng B Zhi Jingtai J Zheng Xiangqian X Gu Lin L Gao Ming M Kong Pengzhou P Zhang Jun J

Cell death & disease 20201009 10

Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be signific ...[more]

PMID: 33037185

Similar Datasets

Project description:Ornithine decarboxylase (ODC) plays an indispensable role in the process of polyamine biosynthesis. Polyamines are a pivotal part of living cells and have diverse roles in the regulation of cell proliferation and apoptosis, aging and reproduction. However, to date, there have been no reports about ODC regulating follicular development in goose ovaries. Here, we constructed ODC siRNA and overexpression plasmids and transfected them into goose primary granulosa cells (GCs) to elucidate the effects of ODC interference and overexpression on the polyamine metabolism, hormone levels, cell apoptosis and proliferation of granulosa cells. After interfering with ODC in GCs, the mRNA and protein levels of ODC and the content of putrescine were greatly decreased (P < 0.05). When ODC was overexpressed, ODC mRNA and protein levels and putrescine content were greatly increased (P < 0.05). The polyamine-metabolizing enzyme genes ornithine decarboxylase antizyme 1 (OAZ1) and spermidine / spermine-N1-acetyltransferase (SSAT) were significantly increased, and spermidine synthase (SPDS) was significantly decreased when ODC was downregulated (P < 0.05). OAZ1, SPDS and SSAT were significantly increased when ODC was upregulated (P < 0.05). In addition, after interference with ODC, progesterone (P4) levels in the culture medium of GCs increased greatly (P < 0.05), while the overexpression of ODC caused the P4 level to decrease significantly (P < 0.05). After ODC downregulation, granulosa cell activity was significantly reduced, the apoptosis rate was significantly increased, and the BCL-2 / BAX ratio was downregulated (P < 0.05). Under ODC overexpression, the activity of GCs was notably increased, the apoptosis rate was significantly reduced, and the BCL-2 / BAX protein ratio was upregulated (P < 0.05). Our study successfully induced ODC interference and overexpression in goose ovarian GCs, and ODC regulated mainly putrescine content in GCs with a slight influence on spermidine and spermine. Moreover, ODC participated in the adjustment of P4 levels in the culture medium of GCs, promoted granulosa cell proliferation and inhibited granulosa cell apoptosis.

Dataset Information

FATS regulates polyamine biosynthesis by promoting ODC degradation in an ER?-dependent manner in non-small-cell lung cancer.

Publications

FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets