CircRNA WHSC1 targets the miR‐646/NPM1 pathway to promote the development of endometrial cancer

Liu, Yao; Chen, Shuo; Zong, Zhi‐Hong; Guan, Xue; Zhao, Yang

doi:10.1111/jcmm.15346

Cited by 73 publications

(62 citation statements)

References 30 publications

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“…This systematic review identified 105 original articles and two literature reviews reporting the expression pattern of miRNAs [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ,…”

Section: Resultsmentioning

confidence: 99%

MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review

Favier

Rocher

Larsen

et al. 2021

Cancers

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The objective of this systematic review is to summarize our current knowledge on the influence of miRNAs in the epigenetic deregulation of tumor-related genes in endometrial cancer (EC). We conducted a literature search on the role of miRNAs in the epigenetic regulation of EC applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following terms were used: microRNA, miRNA, miR, endometrial cancer, endometrium, epigenetic, epimutation, hypermethylation, lynch, deacetylase, DICER, novel biomarker, histone, chromatin. The miRNAs were classified and are presented according to their function (tumor suppressor or onco-miRNA), their targets (when known), their expression levels in EC tissue vs the normal surrounding tissue, and the degree of DNA methylation in miRNA loci and CpG sites. Data were collected from 201 articles, including 190 original articles, published between November 1, 2008 and September 30, 2020 identifying 313 different miRNAs implicated in epigenetic regulation of EC. Overall, we identified a total of 148 miRNAs with decreased expression in EC, 140 miRNAs with increased expression in EC, and 22 miRNAs with discordant expression levels. The literature implicated different epigenetic phenomena including altered miRNA expression levels (miR-182, -230), changes in the methylation of miRNA loci (miR-34b, -129-2, -130a/b, -152, -200b, -625) and increased/decreased methylation of target genes (miR-30d,-191). This work provides an overview of all miRNAs reported to be involved in epigenetic regulation in EC including DNA methylation and RNA-associated silencing. These findings may contribute to novel strategies in diagnosis, risk assessment, and treatments aimed at miRNAs, their target genes or DNA methylation.

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Section: Resultsmentioning

confidence: 99%

MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review

Favier

Rocher

Larsen

et al. 2021

Cancers

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“…25 In endometrial cancer, circWHSC1 was aberrantly enhanced, and promoted cell proliferation and motility and inhibited apoptosis in vitro and contributed to tumour formation in vivo. 26 In this study, the functional roles of circWHSC1 in HCC were determined for the first time. Our data exhibited that circWHSC1 level was raised in HCC.…”

Section: Discussionmentioning

confidence: 98%

CircWHSC1 serves as an oncogene to promote hepatocellular carcinoma progression

Lyu

Zhai

Hao

et al. 2021

Eur J Clin Investigation

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Background: Circular RNAs (circRNAs) function as vital regulators in multifarious cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNA Wolf-Hirschhorn syndrome candidate gene-1 (circWHSC1) in HCC are barely known. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted for the levels of circWHSC1, miR-142-3p, miR-421, miR-665 and homeobox A1 (HOXA1) mRNA. Cell Counting Kit-8 (CCK-8) assay, colony formation assay and 5′-ethynyl-2′-deoxyuridine (EdU) assay were used to evaluate cell proliferation ability. Transwell assay was adopted for cell migration and invasion. Western blot assay was employed for protein levels. RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were executed to verify the interaction between miR-142-3p and circWHSC1 or HOXA1. Murine xenograft model assay was conducted for the role of circWHSC1 in vivo. The morphology of exosomes was observed by transmission electron microscopy (TEM). Results: CircWHSC1 was elevated in HCC tissues and cells, and high level of circWHSC1 was associated with worse overall survival of HCC patients. Knockdown of circWHSC1 suppressed HCC cell proliferation and metastasis in vitro and restrained tumorigenesis in vivo. CircWHSC1 functioned as the sponge for miR-142-3p, which directly targeted HOXA1. Inhibition of miR-142-3p ameliorated the effects of circWHSC1 knockdown on HCC cell proliferation and metastasis. Moreover, miR-142-3p overexpression restrained the growth and motility of HCC cells, with HOXA1 elevation reversing the impacts. Additionally, circWHSC1 was increased in HCC patients' serum and might be a diagnostic indicator for HCC. Conclusion: CircWHSC1 played a tumour-promoting role in HCC by elevating HOXA1 through sponging miR-142-3p.

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“…A recent study by Liu et al suggested that overexpression of Cir-c_WHSC1 promoted the proliferation and invasiveness of cells through the miR-646/NPM1 axis. 33 Likewise, another circRNA, Circ_PUM1, was reported to trigger malignant behaviors of EC cells through targeting miR-136/NOTCH3. 34 Here, our study confirmed a similar role of Circ_0109046 in the progression of EC.…”

Section: Discussionmentioning

confidence: 99%

“…It was found that downregulation of Circ_0109046 in AN3‐CA cells decreased cell proliferation and aggressiveness but increased cell apoptosis, while overexpression of Circ_0109046 in HEC‐1‐A led to reversed trends. A recent study by Liu et al suggested that overexpression of Circ_WHSC1 promoted the proliferation and invasiveness of cells through the miR‐646/NPM1 axis 33 . Likewise, another circRNA, Circ_PUM1, was reported to trigger malignant behaviors of EC cells through targeting miR‐136/NOTCH3 34 .…”

Section: Discussionmentioning

confidence: 99%

Circ_0109046 promotes the malignancy of endometrial carcinoma cells through the microRNA‐105/SOX9/Wnt/β‐catenin axis

Liu

Piao

et al. 2020

IUBMB Life

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Emerging evidence suggests the important involvements of circular RNAs (cir-cRNAs) in cancer progression. This study focuses on the function of Circ_0109046 on the malignancy of endometrial carcinoma (EC) cells and the molecules involved. First, high expression of Circ_0109046 was found in EC tissues compared to the adjacent tissues, and it predicted unfavorable prognosis in patients. Similarly, high expression of Circ_0109046 was confirmed in EC cells relative to that in normal endometrial epithelial cells. Silencing of Circ_0109046 in AN3-CA cells inhibited proliferation and aggressiveness but increased apoptosis of cells. Circ_0109046 was mainly sub-localized in cytoplasm, and it mediated SOX9 expression through sponging microRNA (miR)-105. The proliferation and aggressiveness of EC cells suppressed by Circ_0109046 downregulation was recovered upon SOX9 overexpression. SOX9 activated the Wnt/β-catenin pathway. Furthermore, downregulation of Circ_0109046 reduced the growth of xenograft tumors in nude mice. This study evidenced that Circ_0109046 upregulates SOX9 expression through sponging miR105, leading to activation of Wnt/β-catenin signaling and the malignant growth of EC. This study may offer novel understanding in EC treatment.

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CircRNA WHSC1 targets the miR‐646/NPM1 pathway to promote the development of endometrial cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 73 publications

References 30 publications

MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review

MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review

CircWHSC1 serves as an oncogene to promote hepatocellular carcinoma progression

Circ_0109046 promotes the malignancy of endometrial carcinoma cells through the microRNA‐105/SOX9/Wnt/β‐catenin axis

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