Circular RNA expression in extracellular vesicles isolated from serum of patients with endometrial cancer

Xu, Hanzi; Gong, Zhen; Shen, Yang; Fang, Yichen; Zhong, Shanliang

doi:10.2217/epi-2017-0109

Cited by 90 publications

(76 citation statements)

References 47 publications

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“…Considering the relatively low abundance of circRNAs and the various miRNA binding sites within mRNA and circRNA transcripts, sponging multiple miRNAs by a single circRNA could be a general mechanism in cells . Through bioinformatics analysis (miRanda software, the CircInteractome database, and RNAhybrid software), we undertook a miRNA pull‐down assay using biotin‐coupled miRNA mimics (miR‐182, miR‐93, miR‐1205, and miR‐557; Figures D and ). Interestingly, circCRIM1 was only efficiently enriched with miR‐182 and miR‐93, but not the other miRs (Figure C).…”

Section: Resultsmentioning

confidence: 99%

Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

et al. 2019

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In recent years, circular RNAs (circRNAs) have been revealed to have important roles in carcinogenesis. Metastasis is the leading cause of lung adenocarcinoma (LUAC) death. However, the contributions of circRNA to the metastasis of LUAC remain largely unknown. Based on circBase data and our biobank tissues, we identified circCRIM1 (a circRNA derived from exons 2, 3 and 4 of the CRIM1 gene, hsa_circ_0002346) as having a significantly decreased expression in LUAC samples compared with matched normal control samples. Both in vivo and in vitro experiments revealed that circCRIM1 suppresses the invasion and metastasis of LUAC. In vitro precipitation of circRNAs, luciferase reporter assay, and biotin‐coupled microRNA capture were carried out to investigate the Ago2‐dependent interaction of circCRIM1 and microRNA (miR)‐93/miR‐182. Mechanistically, we found that circCRIM1 could promote the expression of leukemia inhibitory factor receptor, a well‐known tumor suppressor, by sponging miR‐93 and miR‐182. In the clinical and pathological analyses, the downregulation of circCRIM1 in LUAC was significantly correlated with lymphatic metastasis and TNM stage, which served as an independent risk factor for the overall survival of patients with LUAC. Our study showed that circCRIM1 inhibits the invasion and metastasis of lung adenocarcinoma cancer cells, which makes it a potential therapeutic target.

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Section: Resultsmentioning

confidence: 99%

Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

et al. 2019

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“…CircRNA has been considered to be essential in the carcinogenesis and tumor progression of EC 23 . Besides, some studies also suggest that it could be a biomarker candidate for diagnosis and treatment of EC 33,34 . However, the function of circRNAs in MPA resistance remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Hsa-circ-0001860 promotes Smad7 to enhance MPA resistance in endometrial cancer via miR-520h

Yuan

Zheng

Zeng

et al. 2020

Preprint

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Background Medroxyprogesterone acetate (MPA) is one of the most commonly prescribed progestin for the treatment of endometrial cancer (EC). Despite initial benefits, many patients ultimately develop progesterone resistance. Circular RNA (circRNA) is a kind of noncoding RNA, contributing greatly to the development of human tumor. However, the role of circular RNA in MPA resistance is unknown. Methods We explored the expression profile of circRNAs in Ishikawa cells treated with (ISK/MPA) or without MPA (ISK) by RNA sequencing, and identified a key circRNA hsa_circ_0001860. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify its expression in MPA-resistant cell lines and tissues. CCK8, Transwell and flow cytometry were used to evaluate the functional roles of hsa_circ_0001860 in MPA resistance. The interaction between hsa_circ_0001860 and miR-520h was confirmed by bioinformatics analysis and luciferase reporter assay. Results The expression of hsa_circ_0001860 was significantly downregulated in MPA-resistant cell lines and tissues, and negatively correlated with lymph node metastasis and histological grade of EC. Functional analysis showed that hsa_circ_0001860 knockdown by shRNA promoted the proliferation, migration and invasion and inhibited the apoptosis of Ishikawa cells treated with MPA. Mechanistically, hsa_circ_0001860 promoted Smad7 expression by sponging miR-520h. Conclusion Hsa_circ_0001860 plays an important role in the development of MPA resistance in EC through miR-520h / Smad7 axis, and it could be targeted to reverse the MPA resistance in endometrial cancer.

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“…Circular RNAs (circRNAs) exist widely in various organisms and are aberrantly expressed in epithelial tumors, such as bladder (17), breast cancer (18), basal cell carcinoma (19) and colorectal cancer (20) and in stromal tumors, such as glioma (21). Studies have reported that circRNAs are enriched in extracellular vesicles (EVs) isolated from liver cancer or serum of endometrial cancer patients (10,11,20). Xu et al found that the number of upregulated circRNAs was more than the number of downregulated circRNAs in EVs from patients with endometrial cancer (11).…”

Section: Discussionmentioning

confidence: 99%

“…MENGJIE ZHAO 1* , JINJIN XU 2* , SHANLIANG ZHONG 3 , YUCHI LIU 4 , HONG XIAO 1 , LIANGYUAN GENG 4 and HONGYI LIU 4 also found differential expression of circRNAs in EVs isolated from the serum of patients with endometrial cancer when compared with normal controls (11). A recent study demonstrated that exosomal circRNAs from arsenite-transformed cells were involved in the malignant transformation of human hepatic cells (12).…”

Section: Expression Profiles and Potential Functions Of Circular Rnasmentioning

confidence: 99%

Expression profiles and potential functions of circular RNAs in extracellular vesicles isolated from radioresistant glioma cells

Zhao

Zhong

et al. 2019

Oncol Rep

Self Cite

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The molecular mechanisms of circular RNAs (circRNAs) in extracellular vesicles (EVs) associated with glioma radioresistance remain unknown. The aim of the present study was to assess the differential circRNA expression profiles between EVs isolated from U251 cells and EVs isolated from radioresistant U251 (RR-U251) cells. Identified circRNAs in EVs isolated from RR-U251 cells (RR-EVs) act as a U251 microRNA (miRNA) sponge. The circRNA expression was determined using RNA sequencing (RNA-seq) technique. A total of 1,235 circRNAs were detected. We identified 63 upregulated and 48 downregulated circRNAs in RR-EVs compared with those from U251 cells (Nor-EVs). The expression level of candidate circATP8B4 was confirmed using real-time quantitative PCR. It was significantly higher in RR-EVs than in Nor-EVs. Expression profile of RR-U251 and U251 miRNAs was conducted. miRanda and RNAhybrid softwares was used to predict the U251 downregulated miRNAs interacting with circATP8B4. CircATP8B4 from RR-EVs may be transferred to normal glioma U251 cells and act as an miR-766 sponge to promote cell radioresistance. In conclusion, using RNA-seq and bioinformatics, it was found that circATP8B4 in RR-EVs acts as a U251 miR-766 sponge, which may be involved in glioma radioresistance.

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Circular RNA expression in extracellular vesicles isolated from serum of patients with endometrial cancer

Abstract: We identified 275 differentially expressed circRNAs and the expression level of two circRNAs was confirmed using real-time quantitative PCR.

Cited by 90 publications

References 47 publications

Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

Hsa-circ-0001860 promotes Smad7 to enhance MPA resistance in endometrial cancer via miR-520h

Expression profiles and potential functions of circular RNAs in extracellular vesicles isolated from radioresistant glioma cells

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