circPTEN1, a circular RNA generated from PTEN, suppresses cancer progression through inhibition of TGF-β/Smad signaling DOI Creative Commons
Lin Zheng, Hui Liang, Qiaoling Zhang

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 8, 2022

Abstract Background PTEN is one of the most frequently mutated genes in human cancer. Although roles canonical protein and isoforms have been extensively explored, current understanding family members cannot fully illustrate diversity their biological processes tumor development. Notably, function noncoding RNAs arising from has less elucidated. Methods We searched circBase circInteractome to analyze potential for generating circRNAs. Then, Sanger sequencing, RNase R Actinomycin D assays were used verify ring structure circPTEN1. In situ hybridization qRT-PCR determine level circPTEN1 peritumor tissues colorectal cancer (CRC). Furthermore, functional experiments, including Transwell assay, 3D multicellular spheroid invasion assay metastasis models, performed using knockdown overexpression cell lines vitro vivo investigate effects on CRC. Mechanistically, luciferase reporter fluorescence hybridization, electrophoretic mobility shift RNA immunoprecipitation, pull-down mass spectrometry executed. Results identified a circular generated gene, designated circPTEN1, that downregulated cancer, decreased expression predicts poor survival. Low promotes PDX models accelerates vitro, whereas reveals opposite roles. Mechanically, we found capable binding MH2 domain Smad4 disrupt its physical interaction with Smad2/3, which reduces formation subsequent nucleus translocation Smad complexes consequently suppresses downstream associated epithelial-mesenchymal transition upon TGF-β stimulation. eIF4A3 cyclization by directly flanking region. Conclusions Our study uncovered novel gene-generated circRNA suppression function, further revealed mechanism CRC mediated TGF-β. The identification provides new direction investigation, elucidation circPTEN1/TGF-β/Smad signaling may pave way development therapeutic strategy progression.

Language: Английский

The expanding regulatory mechanisms and cellular functions of circular RNAs DOI
Ling‐Ling Chen

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(8), P. 475 - 490

Published: May 4, 2020

Language: Английский

Citations

1183
Circular RNA: metabolism, functions and interactions with proteins DOI Creative Commons

Wei‐Yi Zhou,

Zerong Cai, Jia Liu

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Dec. 1, 2020

Circular RNAs (CircRNAs) are single-stranded, covalently closed RNA molecules that ubiquitous across species ranging from viruses to mammals. Important advances have been made in the biogenesis, regulation, localization, degradation and modification of circRNAs. CircRNAs exert biological functions by acting as transcriptional regulators, microRNA (miR) sponges protein templates. Moreover, emerging evidence has revealed a group circRNAs can serve decoys, scaffolds recruiters. However, existing research on circRNA-protein interactions is quite limited. Hence, this review, we briefly summarize recent progress metabolism elaborately discuss patterns interactions, including altering between proteins, tethering or sequestering recruiting proteins chromatin, forming circRNA-protein-mRNA ternary complexes translocating redistributing proteins. Many discoveries unique expression signatures play crucial roles variety diseases, enabling them potentially act diagnostic biomarkers therapeutic targets. This review systematically evaluates mechanisms circRNAs, with hope advancing translational medicine involving

Language: Английский

Citations

890
RNA in cancer DOI
Gregory J. Goodall, Vihandha O. Wickramasinghe

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 21(1), P. 22 - 36

Published: Oct. 20, 2020

Language: Английский

Citations

839
Circular RNAs: Characterization, cellular roles, and applications DOI Creative Commons

Chu‐Xiao Liu,

Ling‐Ling Chen

Cell, Journal Year: 2022, Volume and Issue: 185(12), P. 2016 - 2034

Published: May 17, 2022

Language: Английский

Citations

639
Lipid metabolism and cancer DOI Creative Commons
Xueli Bian, Rui Liu, Ying Meng

et al.

The Journal of Experimental Medicine, Journal Year: 2020, Volume and Issue: 218(1)

Published: Dec. 18, 2020

Dysregulation in lipid metabolism is among the most prominent metabolic alterations cancer. Cancer cells harness to obtain energy, components for biological membranes, and signaling molecules needed proliferation, survival, invasion, metastasis, response tumor microenvironment impact cancer therapy. Here, we summarize discuss current knowledge about advances made understanding regulation of introduce different approaches that have been clinically used disrupt

Language: Английский

Citations

638
Circular RNAs in Cancer: Biogenesis, Function, and Clinical Significance DOI
Jiao Li, Dan Sun, Wenchen Pu

et al.

Trends in cancer, Journal Year: 2020, Volume and Issue: 6(4), P. 319 - 336

Published: Feb. 19, 2020

Language: Английский

Citations

556
circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity DOI Creative Commons

Botai Li,

Lili Zhu,

Chunlai Lu

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 12, 2021

Abstract Circular RNAs (circRNA) are a class of covalently closed single-stranded that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated non-small cell lung (NSCLC) tissues, and negatively correlate with NSCLC malignant features. Elevated inhibits growth metastasis cells. Mechanistically, functions as scaffold enhance the interaction between TRIM25 IGF2BPs, positive regulator tumor progression metastasis. This TRIM25/circNDUFB2/IGF2BPs ternary complex facilitates ubiquitination degradation this effect enhanced by N 6 -methyladenosine (m A) modification . Moreover, is also recognized RIG-I activate RIG-I-MAVS signaling cascades recruit immune cells into microenvironment (TME). Our data thus provide evidences participates IGF2BPs activation anti-tumor immunity during via modulation both protein degradation, well cellular responses.

Language: Английский

Citations

440
Trends in insulin resistance: insights into mechanisms and therapeutic strategy DOI Creative Commons

Mengwei Li,

Xiaowei Chi, Ying Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 6, 2022

The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into medically manageable chronic condition. Insulin is key peptide hormone and mediates the systemic glucose metabolism in different tissues. resistance (IR) disordered biological response for stimulation through disruption molecular pathways target Acquired conditions genetic factors have been implicated IR. Recent biochemical studies suggest that dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids toxic lipid metabolites promote IR other associated with several groups abnormal syndromes include obesity, diabetes, dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), abnormalities. Although no medication specifically approved treat IR, we summarized lifestyle changes pharmacological medications used as efficient intervention improve sensitivity. Ultimately, systematic discussion complex mechanism will help identify potential new targets closely

Language: Английский

Citations

428
NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications DOI Creative Commons
Huai‐Qiang Ju,

Jin‐Fei Lin,

Tian Tian

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 7, 2020

Abstract Nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms, and provides the reducing power for anabolic reactions redox balance. NADPH homeostasis regulated by varied signaling pathways several metabolic enzymes that undergo adaptive alteration cancer cells. The reprogramming of renders cells both highly dependent on this network antioxidant capacity more susceptible to oxidative stress. Modulating unique might be effective strategy eliminate these In review, we summarize current existing literatures homeostasis, including its biological functions, regulatory mechanisms corresponding therapeutic interventions human cancers, providing insights into implications targeting metabolism associated mechanism therapy.

Language: Английский

Citations

372
Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output DOI Creative Commons

Qiyi Zhao,

Jiayu Liu,

Hong Deng

et al.

Cell, Journal Year: 2020, Volume and Issue: 183(1), P. 76 - 93.e22

Published: Sept. 14, 2020

Language: Английский

Citations

341