CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA

Yang, Xiaowei; Zhao, Lu; Pei, Jing; Wang, Zhaorui; Zhang, Jingjie; Wang, Benzhong

doi:10.1007/s10549-020-05753-9

Cited by 21 publications

(18 citation statements)

References 34 publications

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“…Although CELF6 has been shown to regulate alternative splicing (Ladd et al, 2004), we find very few significant targets outside of 3 0 UTR regions, suggesting that CELF6 in the brain may be more involved with post-transcriptional regulation. UTR binding is consistent with recent work showing CELF6 is able to regulate the stability of p21 (Liu et al, 2019) and FBP (Yang et al, 2020) in cancer cells. We found very few changes to splicing in Celf6 KO mice (not shown; available at GEO: GSE160293) and few effects to TE, suggesting that CELF6 acts on its brain targets primarily to enhance mRNA degradation.…”

Section: Discussionsupporting

confidence: 91%

CLIP and Massively Parallel Functional Analysis of CELF6 Reveal a Role in Destabilizing Synaptic Gene mRNAs through Interaction with 3′ UTR Elements

et al. 2020

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Section: Discussionsupporting

confidence: 91%

CLIP and Massively Parallel Functional Analysis of CELF6 Reveal a Role in Destabilizing Synaptic Gene mRNAs through Interaction with 3′ UTR Elements

et al. 2020

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“…Molecular heterogeneity is prominent in the TNBC subtype, and is reflected by the obvious prognostic and patient's sensitivity to chemotherapy treatment, which is the only available systemic therapy currently (1). Although TNBC patients benefit from standard chemotherapy, they still face a high recurrence rate and a high possibility of drug resistance, leaving TNBC a major challenge in the clinic (4,6). Clinical trial data show that gefitinib is well tolerated in patients with a wide range of tumor types (7).…”

Section: Introductionmentioning

confidence: 99%

Role of GPX4-Mediated Ferroptosis in the Sensitivity of Triple Negative Breast Cancer Cells to Gefitinib

et al. 2020

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Gefitinib resistance in triple negative breast cancer (TNBC) is a growing important concern. Glutathione peroxidase 4 (GPX4) is a main regulator of ferroptosis, which is pivotal for TNBC cell growth. We investigated GPX4-mediated ferroptosis in gefitinib sensitivity in TNBC. Gefitinib resistant TNBC cells MDA-MB-231/Gef and HS578T/Gef were constructed and treated with lentivirus sh-GPX4 and ferroptosis inhibitor ferrostatin-1. GPX4 expression, cell viability and apoptosis were detected. Malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) levels were evaluated. The levels of ferroptosis-related proteins were detected. Subcutaneous tumor model was established in nude mice, and gefitinib was intraperitoneally injected to evaluate tumor growth, apoptosis, and Ki-67 expression. GPX4 was increased in gefitinib-resistant cells. After silencing GPX4, the inhibition rate of cell viability was increased, the limitation of colony formation ability was reduced, apoptosis rate was increased, and the sensitivity of cells to gefitinib was improved. After silencing GPX4, MDA and ROS production were increased, while GSH was decreased. Silencing GPX4 promoted ferroptosis. Inhibition of GPX4 promoted gefitinib sensitivity by promoting cell ferroptosis. In vivo experiments also revealed that inhibition of GPX4 enhanced the anticancer effect of gefitinib through promoting ferroptosis. Overall, inhibition of GPX4 stimulated ferroptosis and enhanced TNBC cell sensitivity to gefitinib.

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“…The multifunctional p21 protein plays a significant part in cell cycle progression, cell senescence, apoptosis, and transcriptional regulation [118,119]. Moreover, the stabilization of FBP1 mRNA by CELF6 leads to suppressed cell proliferation, cell migration, and cell invasion in triple-negative breast cancer [120]. FBP1 performs a tumor suppressor function by limiting glucose uptake and glycolysis [121].…”

Section: Other Celf Membersmentioning

confidence: 99%

CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis

Aghdam

Jave‐Suárez

2021

IJMS

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Post-transcriptional modifications to coding and non-coding RNAs are unquestionably a pivotal way in which human mRNA and protein diversity can influence the different phases of a transcript’s life cycle. CELF (CUGBP Elav-like family) proteins are RBPs (RNA-binding proteins) with pleiotropic capabilities in RNA processing. Their responsibilities extend from alternative splicing and transcript editing in the nucleus to mRNA stability, and translation into the cytoplasm. In this way, CELF family members have been connected to global alterations in cancer proliferation and invasion, leading to their identification as potential tumor suppressors or even oncogenes. Notably, genetic variants, alternative splicing, phosphorylation, acetylation, subcellular distribution, competition with other RBPs, and ultimately lncRNAs, miRNAs, and circRNAs all impact CELF regulation. Discoveries have emerged about the control of CELF functions, particularly via noncoding RNAs, and CELF proteins have been identified as competing, antagonizing, and regulating agents of noncoding RNA biogenesis. On the other hand, CELFs are an intriguing example through which to broaden our understanding of the RBP/noncoding RNA regulatory axis. Balancing these complex pathways in cancer is undeniably pivotal and deserves further research. This review outlines some mechanisms of CELF protein regulation and their functional consequences in cancer physiology.

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CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA

Cited by 21 publications

References 34 publications

CLIP and Massively Parallel Functional Analysis of CELF6 Reveal a Role in Destabilizing Synaptic Gene mRNAs through Interaction with 3′ UTR Elements

CLIP and Massively Parallel Functional Analysis of CELF6 Reveal a Role in Destabilizing Synaptic Gene mRNAs through Interaction with 3′ UTR Elements

Role of GPX4-Mediated Ferroptosis in the Sensitivity of Triple Negative Breast Cancer Cells to Gefitinib

CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis

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