Overexpression of circRNA circFAT1 in Endometrial Cancer Cells Increases Their Stemness by Upregulating miR-21 Through Methylation

Wu, Weiwei; Zhou, Jian; Wu, Yan; Tang, Xuedong; Zhu, Weili

doi:10.1089/cbr.2020.4506

Cited by 9 publications

(8 citation statements)

References 16 publications

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“…On the other hand, the high expression of miR‐21 has been reported to be associated with chemotherapy resistance, and GEM‐treated CAFs secrete a large amount of exosomes from TME, such as miR‐21, to promote cell proliferation and GEM resistance 13 . What's more, a previous study has also revealed that miR‐21 overexpression enhances cell stemness, while repression of miR‐21 expression reduces cell stemness 41 . In our research, the binding site of HIF‐1α to miR‐21 gene promoter was predicted by JASPAR database and verified by dual‐luciferase reporter gene assay.…”

Section: Discussionmentioning

confidence: 99%

Cancer‐associated fibroblasts promote stemness maintenance and gemcitabine resistance via HIF‐1α/miR‐21 axis under hypoxic conditions in pancreatic cancer

Deng,

Zou,

et al. 2024

Molecular Carcinogenesis

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Gemcitabine (GEM) resistance affects chemotherapy efficacy of pancreatic cancer (PC). Cancer‐associated fibroblasts (CAFs) possess the ability of regulating chemoresistance. This study probed the mechanism of hypoxia‐treated CAFs regulating cell stemness and GEM resistance in PC. Miapaca‐2/SW1990 were co‐cultured with PC‐derived CAFs under normoxic/hypoxic conditions. Cell viability/self‐renewal ability was determined by MTT/sphere formation assays, respectively. Protein levels of CD44, CD133, Oct4, and Sox2 were determined by western blot. GEM tumoricidal assay was performed. PC cell GEM resistance was evaluated by MTT assay. CAFs were cultured at normoxia/hypoxia. HIF‐1α and miR‐21 expression levels were assessed by RT‐qPCR and western blot, with their binding sites and binding relationship predicted and verified. CAF‐extracellular vesicles (EVs) were incubated with Miapaca‐2 cells. The RAS/AKT/ERK pathway activation was detected by western blot. PC xenograft models were established and treated with hypoxic CAF‐EVs and GEM. CAFs and PC cell co‐culture increased cell stemness maintenance, GEM resistance, cell viability, stem cell sphere number, and protein levels of CD44, CD133, Oct4, and Sox2, and weakened GEM tumoricidal ability to PC cells, with the effects further enhanced by hypoxia. Hypoxia induced HIF‐1α and miR‐21 overexpression in CAFs. Hypoxia promoted CAFs to secrete high‐level miR‐21 EVs via the HIF‐1α/miR‐21 axis, and activated the miR‐21/RAS/AKT/ERK pathway. CAF‐EVs promoted GEM resistance in PC via the miR‐21/RAS/ATK/ERK pathway in vivo. Hypoxia promoted CAFs to secrete high‐level miR‐21 EVs through the HIF‐1α/miR‐21 axis, and activated the miR‐21/RAS/AKT/ERK pathway via EVs to trigger stemness maintenance and GEM resistance in PC.

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Section: Discussionmentioning

confidence: 99%

Cancer‐associated fibroblasts promote stemness maintenance and gemcitabine resistance via HIF‐1α/miR‐21 axis under hypoxic conditions in pancreatic cancer

Deng,

Zou,

et al. 2024

Molecular Carcinogenesis

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“…using a similar methodology, circ-FaT atypical cadherin 1 (circFaT1) was shown to be upregulated in ec and its levels were positively correlated with those of mir-21 in ec tissues (88). overexpression of circFaT1 increased mir-21 expression levels by reducing mir-21 gene methylation to increase cancer stem cell characteristics and promote tumor progression (88).…”

Section: Endometrial Cancer (Ec)mentioning

confidence: 99%

Interactions of circRNAs with methylation: An important aspect of circRNA biogenesis and function (Review)

et al. 2022

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circular rna (circrna) molecules are noncoding rnas with unique circular covalently closed structures that contribute to gene expression regulation, protein translation and act as microrna sponges. circrnas also have important roles in human disease, particularly tumorigenesis and antitumor processes. Methylation is an epigenetic modification that regulates the expression and roles of dna and coding rna and their interactions, as well as of noncoding rna molecules. Previous studies have focused on the effects of methylation modification on circRNA expression, transport, stability, translation and degradation of circrnas, as well as how circrna methylation occurs and the influence of circRNAs on methylation modification processes. circRNA and methylation can also regulate disease pathogenesis via these interactions. In the present study, we define the relationship between circrnas and methylation, as well as the functions and mechanisms of their interactions during disease progression. Contents1. introduction 2. literature search strategy 3. dna methylation 4. rna methylation 5. effects of methylation on circrna biological function 6. Study of methylation-modified circRNAs in disease 7. circRNAs influence disease progression via methylation regulation 8. databases related to circrna methylation research 9. conclusion

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“…Liu et al (95) revealed for the first time that the novel circRNA circTNFRSF21 could regulate MAPK13 expression via a competitive interaction with miR-1227, thereby activating the MAPK13/activating transcription factor 2 signaling pathway and promoting the formation of EC. circFAT1 has been revealed to be upregulated in EC, which leads to an increase in the cell stemness viability of cancer cells via upregulation of miR-21 (96). The cytoplasmic polyadenylation element-binding protein (CPEB) family is expressed differently in different types of tumors, thereby exerting an important role in the occurrence and development of tumors.…”

Section: Migration Invasion and Tumor Growthmentioning

confidence: 99%

Circular RNAs in endometrial carcinoma (Review)

et al. 2022

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As one of the leading causes of death in women in Western developed countries, endometrial carcinoma (EC) is a common gynecological malignant tumor that seriously threatens women's health. In recent years, a trend has emerged of EC being manifested in younger women, and its overall incidence is gradually rising. Circular RNAs (circRNAs) are novel endogenous transcripts that have limited ability to encode proteins due to their covalent closed-loop structure, which differs from that of other types of RNA. A growing body of evidence has demonstrated that circRNAs fulfill an important role in lung cancer, gastric cancer, breast cancer, EC and other malignant tumor types, and they can affect the occurrence and development of these malignancies through a variety of pathways, further demonstrating the potential of circRNAs as molecular biomarkers for the diagnosis, treatment and prognosis of malignant tumors. The purpose of the present review is to summarize the current understanding of the biogenesis and effects of circRNAs, and to discuss the expression, function and underlying mechanism of circRNAs in EC in order to identify potential novel biomarkers.

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Overexpression of circRNA circFAT1 in Endometrial Cancer Cells Increases Their Stemness by Upregulating miR-21 Through Methylation

Cited by 9 publications

References 16 publications

Cancer‐associated fibroblasts promote stemness maintenance and gemcitabine resistance via HIF‐1α/miR‐21 axis under hypoxic conditions in pancreatic cancer

Cancer‐associated fibroblasts promote stemness maintenance and gemcitabine resistance via HIF‐1α/miR‐21 axis under hypoxic conditions in pancreatic cancer

Interactions of circRNAs with methylation: An important aspect of circRNA biogenesis and function (Review)

Circular RNAs in endometrial carcinoma (Review)

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