CircRNAs: role in human diseases and potential use as biomarkers

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(5)

Published: May 11, 2021

Circular RNAs (circRNAs) are a class of endogenous characterized by covalent loop structure. In comparison to other types RNAs, the abundance circRNAs is relatively low but due circular configuration, their stability very high. addition, display high degree tissue specificity. The sponging activity toward microRNAs best-described mode action circRNAs. However, ability bind with specific proteins, as well encode short propose alternative functions. This review introduces biogenesis and summarizes roles played in human diseases. These include examples functional several organ-specific cancers, such head neck breast lung cancers. we potential functions diabetes, cardiovascular, neurodegenerative Recently, growing number studies have demonstrated involvement wide spectrum signaling molecular pathways, at same time many different controversial views on role function emerging. We conclude offering cellular homeostasis generated networks comprising non-coding RNA-binding proteins. Accordingly, it predictable that circRNAs, highly stable nature remarkable specificity, will emerge reliable biomarkers disease course treatment efficacy.

Language: Английский

---

Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing

Cancers, Journal Year: 2021, Volume and Issue: 13(5), P. 1102 - 1102

Published: March 4, 2021

Within aggressive malignancies, there usually are the “hypoxic zones”—poorly vascularized regions where tumor cells undergo oxygen deficiency through inadequate blood supply. Besides, hypoxia may arise in tumors as a result of antiangiogenic therapy or transarterial embolization. Adapting to hypoxia, acquire hypoxia-resistant phenotype with characteristic alterations signaling, gene expression and metabolism. Both lack by itself hypoxia-responsive phenotypic modulations render more radioresistant, so that hypoxic serious challenge for radiotherapy. An understanding causes radioresistance would help develop novel ways overcoming this challenge. Molecular targets various approaches radiosensitizing considered present review. It is here analyzed how hypoxia-induced cellular responses involving hypoxia-inducible factor-1, heat shock transcription factor 1, proteins, glucose-regulated epigenetic regulators, autophagy, energy metabolism reprogramming, epithelial–mesenchymal transition exosome generation contribute be inhibited attenuating radioresistance. The pretreatments multitarget inhibition cancer cell adaptation seem promising approach sensitizing carcinomas, gliomas, lymphomas, sarcomas radiotherapy and, also, liver radioembolization.

Language: Английский

---

Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1049 - 1082

Published: Oct. 20, 2022

Reversible, spatial, and temporal regulation of metabolic reprogramming epigenetic homeostasis are prominent hallmarks carcinogenesis. Cancer cells reprogram their metabolism to meet the high bioenergetic biosynthetic demands for vigorous proliferation. Epigenetic dysregulation is a common feature human cancers, which contributes tumorigenesis maintenance malignant phenotypes by regulating gene expression. The epigenome sensitive changes. Metabolism produces various metabolites that substrates, cofactors, or inhibitors enzymes. Alterations in pathways fluctuations intermediate convey information regarding intracellular status into nucleus modulating activity enzymes thus remodeling landscape, inducing transcriptional responses heterogeneous requirements. regulated machinery at both post-transcriptional levels. modifiers, chromatin remodelers non-coding RNAs integral contributors regulatory networks involved cancer metabolism, facilitating transformation. However, significance close connection between epigenetics context has not been fully deciphered. Thus, it will be constructive summarize update emerging new evidence supporting this bidirectional crosstalk deeply assess how abnormalities could exploited optimize treatment paradigms establish therapeutic options. In review, we central mechanisms reciprocally modulate each other elaborate upon major contributions interplays aberrations rewiring initiation development. Finally, highlight potential opportunities hematological malignancies solid tumors targeting epigenetic-metabolic circuit. summary, endeavored depict current understanding coordination these fundamental more comprehensively provide perspectives utilizing targets treatment.

Language: Английский

---

Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10

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

Published: March 29, 2022

Abstract Background Hypoxia has long been considered as a hallmark of solid tumors and is closely associated with tumor progression. Circular RNAs (circRNAs) have identified critical modulator in various cancers. However, the connections between hypoxia circRNAs are largely unknown. Methods Here, we investigated expression profile breast cancer (BC) MCF-7 cells under normoxia using microarray. We novel hypoxia-responsive circRNA named circWSB1, whose pattern, potential diagnostic value prognostic significance were assessed by qRT-PCR situ hybridization. Loss- gain-of-function investigations vivo vitro performed to determine biological functions circWSB1. Mechanistically, chromatin immunoprecipitation dual luciferase reporter assays carried out analyze biogenesis Furthermore, biotin-labeled RNA pull-down, mass spectrometry, immunoprecipitation, fluorescent hybridization, electrophoretic mobility shift, deletion-mapping, co-immunoprecipitation rescue experiments applied investigate interaction circWSB1 Ubiquitin-specific peptidase 10 (USP10) well relationship USP10 p53. Results found that was significantly upregulated BC tissues correlated poor clinical outcomes, which might serve an independent factor for patients. Ectopic promoted proliferation cell vivo. transcriptionally HIF1α response could competitively bind deubiquitinase prevent access p53 cells, leading degradation progression BC. Conclusions Taken together, our findings disclose mechanism hypoxia-inducible interact attenuate mediated stabilization promote BC, providing alternative biomarker therapeutic target

Language: Английский

---

Targeting ACYP1-mediated glycolysis reverses lenvatinib resistance and restricts hepatocellular carcinoma progression

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 69, P. 100976 - 100976

Published: May 17, 2023

Language: Английский

---

Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 953 - 1008

Published: Dec. 16, 2023

Cancer reprogramming is an important facilitator of cancer development and survival, with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation, even under sufficient oxygen supply condition. This metabolic alteration, known as the Warburg effect, serves significant indicator malignant transformation. The effect primarily impacts occurrence by influencing pathway in cells. Key enzymes involved this process include glucose transporters (GLUTs), HKs, PFKs, LDHs, PKM2. Moreover, expression transcriptional regulatory factors proteins, such FOXM1, p53, NF-

Language: Английский

---

Emerging role and clinical applications of circular RNAs in human diseases

Functional & Integrative Genomics, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 28, 2025

Language: Английский

---

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(2)

Published: Feb. 26, 2021

Abstract Mitochondria are essential cellular organelles that involved in regulating energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic metabolic disease closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), which major molecules respond to hypoxia, play important roles development by participating multiple processes, such as proliferation, angiogenesis. The Warburg phenomenon reflects pseudo-hypoxic state activates HIF-1α. In addition, product of the effect, lactate, also induces However, proposed aerobic glycolysis occurs due defect mitochondria. Moreover, both HIFs dysfunction can lead complex reprogramming energy including reduced oxidative increased glucose uptake, enhanced anaerobic glycolysis. Thus, there may be connection between this review, we systematically discuss crosstalk dysfunctions development. Above all, stability activity influenced related tricarboxylic acid cycle, electron transport chain components, respiration, mitochondrial-related proteins. Furthermore, activation affecting functions, capacity, biogenesis, apoptosis, fission, autophagy. general, regulation tumorigenesis part an extensive cooperative network.

Language: Английский

---

The circACTN4 interacts with FUBP1 to promote tumorigenesis and progression of breast cancer by regulating the expression of proto-oncogene MYC

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: June 11, 2021

Abstract Background Recent studies have revealed that circular RNAs (circRNAs) play significant roles in the occurrence and development of many kinds cancers including breast cancer (BC). However, potential functions most circRNAs molecular mechanisms underlying progression BC remain elusive. Method Here, Circular RNA microarray was executed 4 pairs tissues para-cancer tissues. The expression prognostic significance circACTN4 cells were determined by qRT-PCR situ hybridization. Gain-and loss-of-function experiments implemented to observe impacts on growth, invasion, metastasis vitro vivo. Mechanistically, chromatin immunoprecipitation, luciferase reporter, pulldown, mass spectrum, fluorescence hybridization co-immunoprecipitation assays executed. Results CircACTN4 significantly upregulated cells, its correlated with clinical stage poor prognosis patients BC. Ectopic strikingly facilitated Whereas knockdown opposite roles. mainly distributed nucleus. Further mechanistic research proved could competitively bind far upstream element binding protein 1 (FUBP1) prevent combination between FUBP1 FIR, thereby activating MYC transcription facilitating tumor cancer. Furthermore, we found factor 2 (USF2) might promote biogenesis circACTN4. Conclusion Our findings uncover a pivotal mechanism mediated USF2 interact via enhancing MYC. be novel target for diagnosis treatment

Language: Английский

---

Carcinoma-associated fibroblasts derived exosomes modulate breast cancer cell stemness through exonic circHIF1A by miR-580-5p in hypoxic stress

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: June 12, 2021

Abstract Hypoxia is a common phenomenon in solid tumors. The roles of exosomes from hypoxic breast cancer stroma are less studied. So, the study was aimed to investigate role cancer-associated fibroblasts (CAFs) cells cancer. circRNA array analysis performed screen differential expressed circRNAs between and normoxic CAFs exosomes. Candidate circHIF1A (circ_0032138) screened out it confirmed that up-regulated their Through investigating cellular functions including cell proliferation stem features, demonstrated transferred into cells, which played an important properties sponging miR-580-5p by regulating CD44 expression. In summary, CircHIF1A may act as target molecule therapy.

Language: Английский

---