Long non-coding RNA FGF13-AS1 inhibits glycolysis and stemness properties of breast cancer cells through FGF13-AS1/IGF2BPs/Myc feedback loop

Ma, Fei; Liu, Xu; Zhou, Shibo; Li, Wenjie; Liu, Chunxiao; Chadwick, Michelle; Cheng, Qian

doi:10.1016/j.canlet.2019.02.008

Cited by 118 publications

(94 citation statements)

References 37 publications

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“…FGF13-AS1 may play a critical role in the glycolytic reprogramming of breast CSCs. This lncRNA is downregulated in breast tumors and inhibits glycolysis and stemness by reducing the half-life of c-Myc mRNA (54). Stemness-associated c-Myc is a transcription factor and target of HIF-1α and induces the expression of glycolytic genes, leading to altered glucose consumption (72).…”

Section: Non-coding Rnas As Mediators Of Breast Cancer Stem Metabolicmentioning

confidence: 99%

The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

et al. 2019

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Within heterogeneous tumors, cancer stem cell (CSC) populations exhibit the greatest tumor initiation potential, promote metastasis, and contribute to therapy resistance. For breast cancer specifically, CSCs are identified by CD44 high CD24 low cell surface marker expression and increased aldehyde dehydrogenase activity. In general, bulk breast tumor cells possess altered energetics characterized by aerobic glycolysis. In contrast, breast CSCs appear to have adaptive metabolic plasticity that allows these tumor-initiating cells to switch between glycolysis and oxidative phosphorylation, depending on factors present in the tumor microenvironment (e.g., hypoxia, reactive oxygen species, availability of glucose). In this article, we review the regulatory molecules that may facilitate the metabolic plasticity of breast CSCs. These regulatory factors include epigenetic chromatin modifiers, non-coding RNAs, transcriptional repressors, transcription factors, energy and stress sensors, and metabolic enzymes. Furthermore, breast cancer cells acquire CSC-like characteristics and altered energetics by undergoing epithelial-mesenchymal transition (EMT). This energy costly process is paired with reprogrammed glucose metabolism by epigenetic modifiers that regulate expression of both EMT and other metabolism-regulating genes. The survival advantage imparted to breast CSCs by metabolic plasticity suggests that targeting the factors that mediate the energetic switch should hinder tumorigenesis and lead to improved patient outcomes.

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Section: Non-coding Rnas As Mediators Of Breast Cancer Stem Metabolicmentioning

confidence: 99%

The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

et al. 2019

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“…While previous study has shown that IMP3 proteins was protein partner of RNAs or proteins to regulate glycolysis level of cancer cells [38][39]. Thus, we investigated the role of circCDKN2B-AS1 in modulating glycolysis in cervical cancer cells.…”

Section: Circcdkn2b-as1 Cooperates With Imp3 To Promotes Glycolysis Omentioning

confidence: 93%

CircCDKN2B-AS1 Interacts with IMP3 to Stabilize Hexokinase 2 mRNA and Facilitate Cervical Squamous Cell Carcinoma Aerobic Glycolysis Progression

Zhang

Zhao

Yang

et al. 2020

Preprint

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Background: Circular RNAs(circRNAs) have been reported to play key roles in the development of various cancers. However, the biological function and clinical significance of most circRNAs are still elusive. The purpose of this study is to explore the function and mechanism of a certain circRNA named circCDKN2B-AS1 in cervical cancer development, and its potential value in clinic. Methods: The qRT-PCR array was conducted to verify the expression level of circCDKN2B-AS1. CCK8 assay, transwell assay, and FCM were undertaken to detect cellular proliferation, migration, and apoptosis, respectively. Seahorse XFe 96 analyzer was used to measure the glycolysis metabolism level. RNA pulldown, RIP, actinomycin-D adding assay and Western Blot were used to screen and elucidate the potential mechanisms. BALB/c nude mice and zebrafish embryo（AB,WT） were used as animal models to investigate tumorigenesis capability.18FDG-microPET/CT was used to detect the glucose metabolism level of subcutaneous tumor in nude mice. Results: CircCDKN2B-AS1, circular isoform of lncRNA CDKN2B-AS1, was upregulated in cervical cancer and precancer tissues. We found that circCDKN2B-AS1 associated with IMP3 protein depending on a specific binding site and regulated the stability of Hexokinase 2(HK2) mRNA, the rate-limiting enzyme of aerobic glycolysis pathway. The expression level of circCDKN2B-AS1 fated the binding of IMP3 to 3’UTR of HK2 mRNA, consequently affects cell malignant phenotypes and aerobic glycolysis of cervical cancer in vitro and in vivo. Mutant circCDKN2B-AS1 lacking of the IMP3 binding site didn’t have such effects. Utilizing an inhibitory peptide to block the interaction between circCDKN2B-AS1 and IMP3 protein impeded the binding of IMP3 to 3’UTR of HK2 mRNA and suppressed aerobic glycolysis in cervical cancer cells.Conclusions: Our findings demonstrate that circCDKN2B-AS1 facilitates aerobic glycolysis by sponging IMP3 protein to stabilize HK2 mRNA, consequently promotes malignant phenotypes in cervical cancer, which may provide a potential approach for cervical cancer therapeutics.

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“…Immunofluorescent staining assays were performed as previously described 26 . In brief, cells were fixed, permeabilized with 0.5% Triton-100 (Solarbio, China) and blocked with 5% bovine serum albumin.…”

Section: Immunohistochemistry (Ihc) and Immunofluorescent Stainingmentioning

confidence: 99%

UBE2O promotes the proliferation, EMT and stemness properties of breast cancer cells through the UBE2O/AMPKα2/mTORC1-MYC positive feedback loop

Liu

et al. 2020

Cell Death Dis

Self Cite

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Ubiquitin-conjugating enzyme E2O (UBE2O) is a large E2 ubiquitin-conjugating enzyme that possesses both E2 and E3 ligase activities. Ectopic UBE2O overexpression is associated with a variety of human diseases, especially cancers. However, the expression profile and functional biology of UBE2O in human breast cancer (BC) remain unclear. In this study, we found that UBE2O was significantly overexpressed in human BC tissues and cells. Patients with high UBE2O expression tended to have a high risk of metastasis and poor prognosis. In vitro assays revealed that UBE2O promoted BC cell proliferation and epithelial-mesenchymal transformation (EMT) and endowed BC cells with cancer stemness properties (CSPs). UBE2O knockdown in MDA-MB-231 cells suppressed tumour growth and lung metastasis in MDA-MB-231 xenograft mouse models. Mechanistically, UBE2O functioned as a ubiquitin enzyme of AMPKα2, promoting its ubiquitination and degradation and thus activating the mTORC1 signal pathway and contributing to BC oncogenesis and metastasis. Furthermore, as a downstream factor of the UBE2O/AMPKα2/mTORC1 axis, the oncoprotein MYC transcriptionally promoted UBE2O and formed a positive feedback loop in human BC. Collectively, our study demonstrated that UBE2O/AMPKα2/mTORC1-MYC forms a positive feedback loop in human BC cells that regulates BC cell proliferation and EMT and endows BC cells with CSPs.

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Long non-coding RNA FGF13-AS1 inhibits glycolysis and stemness properties of breast cancer cells through FGF13-AS1/IGF2BPs/Myc feedback loop

Cited by 118 publications

References 37 publications

The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

The Flick of a Switch: Conferring Survival Advantage to Breast Cancer Stem Cells Through Metabolic Plasticity

CircCDKN2B-AS1 Interacts with IMP3 to Stabilize Hexokinase 2 mRNA and Facilitate Cervical Squamous Cell Carcinoma Aerobic Glycolysis Progression

UBE2O promotes the proliferation, EMT and stemness properties of breast cancer cells through the UBE2O/AMPKα2/mTORC1-MYC positive feedback loop

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