The Roles of circMTO1 in Cancer

Liu, Wei; Xiong, Yuanyuan; Wan, Renhua; Shan, Renfeng; Li, Jianfeng; Wen, Wu

doi:10.3389/fcell.2021.656258

Cited by 10 publications

(6 citation statements)

References 87 publications

(152 reference statements)

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“…43−45 Notably, the DFHBI fluorescence signal obtained by HeLa cells (Figure 4A, red color) is much higher than that generated by LO2 cells (Figure 4A, blue color), consistent with the upregulation of circMTO1 in human cervical cancer cells. 35,45 The order of circMTO1 expression levels in above five human cell lines is as follows: HeLa > LO2 > MCF-7 > HepG-2 > HCT-116 (Figure 4A), consistent with the previous research studies. 23 Moreover, we employed RT-qPCR to measure the circMTO1 expression level in five human cell lines (Figure S3A).…”

Section: ■ Results and Discussionsupporting

confidence: 89%

“…We investigated the applicability of the proposed biosensor for endogenous circMTO1 assay by measuring five types of human cell lines including human breast cancer cell lines (MCF-7 cells), human colorectal cancer cell lines (HCT-116 cells), hepatocellular carcinoma cell lines (HepG-2 cells), normal human liver cell lines (LO2 cells), and human cervical cancer cell lines (HeLa cells). The DFHBI fluorescence signal generated by LO2 cells (Figure A, blue color) is much higher than those obtained by MCF-7 cells (Figure A, green color), HepG-2 cells (Figure A, orange color), and HCT-116 cells (Figure A, purple color), suggesting the downregulation of circMTO1 in breast cancer cells, hepatocellular carcinoma cells, and human colorectal cancer cells. − Notably, the DFHBI fluorescence signal obtained by HeLa cells (Figure A, red color) is much higher than that generated by LO2 cells (Figure A, blue color), consistent with the upregulation of circMTO1 in human cervical cancer cells. , The order of circMTO1 expression levels in above five human cell lines is as follows: HeLa > LO2 > MCF-7 > HepG-2 > HCT-116 (Figure A), consistent with the previous research studies . Moreover, we employed RT-qPCR to measure the circMTO1 expression level in five human cell lines (Figure S3A).…”

Section: Resultsmentioning

confidence: 91%

“…CircMTO1 is selected as a model target. CircMTO1 is originated from exons of MTO1 located at chromosome 6q13, and it is abnormally expressed in many malignant tumors including hepatocellular carcinoma, cervical carcinoma, breast cancer, and colorectal cancer. , We designed two linear template probes (i.e., template-A and template-B) and two RPA primer probes (i.e., forward primer and reverse primer) (Table S2). This assay consists of three steps: (1) target circMTO1-induced proximity ligation-activated recombinase polymerase amplification, (2) generation of Spinach RNA aptamers induced by cascade transcription amplification, and (3) lighting up of RNA aptamers with DFHBI.…”

Section: Resultsmentioning

confidence: 99%

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Construction of Genetically Encoded Light-Up RNA Aptamers for Label-free and Ultrasensitive Detection of CircRNAs in Cancer Cells and Tissues

Zhao,

Li,

Zhang

et al. 2023

Anal. Chem.

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Circular RNAs (circRNAs) as endogenous non-coding RNAs are characterized by covalently closed circular structures, and they widely exist in mammalian cells. The aberrant expression of circRNAs may result in various diseases. Herein, we demonstrate the construction of genetically encoded light-up RNA aptamers for ultrasensitive and label-free detection of circRNA mitochondrial tRNA translation optimization 1 (circMTO1) in cancer cells and tissues. The lightup RNA aptamers are generated by proximity ligation-activated recombinase polymerase amplification (RPA)-assisted transcription amplification. When circMTO1 is present, it initiates the proximity ligation reaction, activating RPA to produce numerous long double-stranded DNAs containing T7 promoters. Subsequently, the RPA products are identified by T7 RNA polymerase, initiating the transcription amplification reaction to generate abundant Spinach RNA aptamers. Spinach RNA aptamers can bind with DFHBI (3,5-difluoro-4hydroxybenzylidene imidazolidinone) dye to produce a distinct fluorescence signal with near-zero background. This biosensor exhibits excellent selectivity and high sensitivity with a limit of detection of 2.54 aM. It can accurately monitor cellular circMTO1 at the single-cell level and discriminate the expression of circMTO1 between breast cancer patient tissues and healthy tissues. Notably, this biosensor can be employed to measure other nucleic acids by altering the corresponding target recognition sequences, providing a valuable platform for cancer diagnosis and biomedical study.

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Section: ■ Results and Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Construction of Genetically Encoded Light-Up RNA Aptamers for Label-free and Ultrasensitive Detection of CircRNAs in Cancer Cells and Tissues

Zhao,

Li,

Zhang

et al. 2023

Anal. Chem.

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“…For an example, circMTO1 was decreased in hepatocellular carcinoma and could bind with miR-9 to attenuate the inhibitory role of miR-9 on the expression of its target p21 [21]. Subsequent studies revealed that circMTO1 could also sponge miR-760, miR-182-5p, miR-630, miR-92, miR-221, miR-3200-5p, miR-19b-3p, miR-17, miR-199a-3p and miR-6893 [25]. Other circRNAs function as competing endogenous RNA (ceRNA) in cancers have also been studied, such as CDR1as binding with miR-671-5p [26], circPRKCI binding with both miR-545 and miR-589 [27], and circHIPK3 interacting with miR-558 [28].…”

Section: Discussionmentioning

confidence: 99%

circAGFG1 Facilitates the Progression of Non-Triple-Negative Breast Cancer Through miR-143-5p/USP14 Axis

Yang

Chen

2022

Preprint

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Circular RNAs (circRNAs) emerged as a new class of regulators in various human diseases, including breast cancer (BC). Our previous study identified that circAGFG1 could promote triple-negative breast cancer (TNBC) progression. However, the clinical values and functions of circAGFG1 in non-TNBC remain elusive. Here, we applied qRT-PCR in 30 pairs of non-TNBC tissues and para-cancerous tissues and in situ hybridization (ISH) in 346 paraffin-embedded non-TNBC tissues to evaluate the expression pattern and clinical significance of circAGFG1 in non-TNBC. Gain- and loss-of-function studies were carried out to determine the biological function of circAGFG1 in non-TNBC in vitro and in vivo. Mechanistically, RNA pull-down, RNA immunoprecipitation, dual luciferase reporter, fluorescent in situ hybridization assays were employed to validate the interaction between circAGFG1 and miR-143-5p as well as miR-143-5p and USP14. We found that circAGFG1 was markedly increased in non-TNBC tissues as well. Moreover, patient suffering from non-TNBC with a higher expression level of circAGFG1 presents a worse clinical outcome. Multivariate analysis uncovered that high level of circAGFG1 might serve as a standalone risk factor for non-TNBC patients. Functional studies substantiated that enforced expression of circAGFG1 increased the malignance of non-TNBC cells, whereas silencing of circAGFG1 produced the opposite. Mechanistic investigations proved that circAGFG1 sponged miR-143-5p to regulate the level of oncogene USP14, leading to the progression of non-TNBC. Taken together, our data revealed that circAGFG1 could also accelerate the progression of non-TNBC via miR-143-5p/USP14 axis and might provide an alternative target for the diagnosis and treatment of non-TNBC.

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“…CircRNA mitochondrial tRNA translation optimization 1 (circMTO1, hsa_circRNA_0007874/hsa_circRNA_104135) originates from exons 2 and 3 of the MTO1 gene with a 318 bp splice length [ 18 ]. CircMTO1 usually functions as a tumor suppressor and is associated with the progression of multiple tumors [ 19 ], including glioblastoma [ 20 ], gallbladder cancer [ 21 ], lung adenocarcinoma [ 22 ], and HCC [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition

Zhang

Yang

et al. 2021

Cell Death Dis

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CircRNA mitochondrial tRNA translation optimization 1 (circMTO1) functions as a tumor suppressor usually and is related to the progression of many tumors, including hepatocellular carcinoma (HCC). CircMTO1 is downregulated in HCC as compared to adjacent nontumor tissue, which may suppress the HCC progression by certain signal pathways. However, the underlying signal pathway remains largely unknown. The interactions between circMTO1 and miR-541-5p were predicted through bioinformatics analysis and verified using pull-down and dual-luciferase reporter assays. CCK-8, transwell, and apoptosis assays were performed to determine the effect of miR-541-5p on HCC progression. Using bioinformatic analysis, dual-luciferase reporter assay, RT-qPCR, and western blot, ZIC1 was found to be the downstream target gene of miR-541-5p. The regulatory mechanisms of circMTO1, miR-541-5p, and ZIC1 were investigated using in vitro and in vivo rescue experiments. The results depicted that silencing circMTO1 or upregulating miR-541-5p expression facilitated HCC cell proliferation, migration, and invasion and inhibited apoptosis. CircMTO1 silencing upregulated the expression of downstream ZIC1 regulators of the Wnt/β-catenin pathway markers, β-catenin, cyclin D1, c-myc, and the mesenchymal markers N-cadherin, Vimentin, and MMP2, while the epithelial marker E-cadherin was downregulated. MiR-541-5p knockdown had the opposite effect and reversed the effect of circMTO1 silencing on the regulation of downstream ZIC1 regulators. Intratumoral injection of miR-541-5p inhibitor suppressed tumor growth and reversed the effect of circMTO1 silencing on the promotion of tumor growth in HCC. These findings indicated that circMTO1 suppressed HCC progression via the circMTO1/ miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling and epithelial-to-mesenchymal transition, making it a novel therapeutic target.

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The Roles of circMTO1 in Cancer

Cited by 10 publications

References 87 publications

Construction of Genetically Encoded Light-Up RNA Aptamers for Label-free and Ultrasensitive Detection of CircRNAs in Cancer Cells and Tissues

Construction of Genetically Encoded Light-Up RNA Aptamers for Label-free and Ultrasensitive Detection of CircRNAs in Cancer Cells and Tissues

circAGFG1 Facilitates the Progression of Non-Triple-Negative Breast Cancer Through miR-143-5p/USP14 Axis

CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition

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