Circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer: involvement of miR-30c-5p/TCF7 axis

Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for t...

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Published inMolecular cancer Vol. 20; no. 1; pp. 93 - 21
Main Authors Guo, Yaxin, Guo, Yuying, Chen, Chen, Fan, Dandan, Wu, Xiaoke, Zhao, Luyang, Shao, Bo, Sun, Zhenqiang, Ji, Zhenyu
Format Journal Article
LanguageEnglish
Published England BioMed Central Ltd 25.06.2021
BioMed Central
BMC
Subjects
Adult
Aged
Analysis
Angiogenesis
Animals
Biomarkers
Cell proliferation
circ3823
Colorectal cancer
Colorectal cancer (CRC)
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Cytogenetics
Development and progression
Disease Progression
DNA sequencing
Female
Fluorescence in situ hybridization
Gene Expression Regulation, Neoplastic - genetics
Growth
Heterografts
Humans
Immunoprecipitation
Male
Medical research
Medicine, Experimental
Metastases
Metastasis
Methyltransferases
Mice
Mice, Inbred BALB C
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
Myc protein
N6-methyladenosine
N6-methyladenosine (m6A)
Neoplasm Invasiveness - genetics
Neovascularization, Pathologic - genetics
Next-generation sequencing
Nucleotide sequencing
Patients
Proteins
Ribonuclease
Ribonucleic acid
RNA
RNA, Circular - genetics
RNA, Circular - metabolism
Signal Transduction - genetics
T Cell Transcription Factor 1 - genetics
T Cell Transcription Factor 1 - metabolism
Tumors
Tumour progression
Massachusetts
Japan
China
Beijing China
United States > US
Tumour progression
Angiogenesis
N6-methyladenosine (m6A)
circ3823
Colorectal cancer (CRC)
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Abstract Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.
AbstractList Abstract Background Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. Methods High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Results Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Conclusions Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.
Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown.BACKGROUNDColorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown.High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823.METHODSHigh-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823.Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823.RESULTSCirc3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823.Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.CONCLUSIONSOur findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.
Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.
Background Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. Methods High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Results Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Conclusions Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.
Background Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. Methods High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Results Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Conclusions Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823. Keywords: Colorectal cancer (CRC), Tumour progression, Angiogenesis, circ3823, N6-methyladenosine (m6A)
Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.
ArticleNumber 93
Audience Academic
Author Chen, Chen
Sun, Zhenqiang
Ji, Zhenyu
Guo, Yuying
Fan, Dandan
Shao, Bo
Guo, Yaxin
Zhao, Luyang
Wu, Xiaoke
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  fullname: Ji, Zhenyu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34172072$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords Tumour progression
Angiogenesis
N6-methyladenosine (m6A)
circ3823
Colorectal cancer (CRC)
Language English
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– volume: 9
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  issue: 13
  year: 2019
  ident: 1372_CR52
  publication-title: Theranostics.
  doi: 10.7150/thno.31868
– volume: 26
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  publication-title: Cell
  doi: 10.1016/j.cell.2017.03.031
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Snippet Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients....
Background Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of...
Abstract Background Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival...
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StartPage 93
SubjectTerms Adult
Aged
Analysis
Angiogenesis
Animals
Biomarkers
Cell proliferation
circ3823
Colorectal cancer
Colorectal cancer (CRC)
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Cytogenetics
Development and progression
Disease Progression
DNA sequencing
Female
Fluorescence in situ hybridization
Gene Expression Regulation, Neoplastic - genetics
Growth
Heterografts
Humans
Immunoprecipitation
Male
Medical research
Medicine, Experimental
Metastases
Metastasis
Methyltransferases
Mice
Mice, Inbred BALB C
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
Myc protein
N6-methyladenosine
N6-methyladenosine (m6A)
Neoplasm Invasiveness - genetics
Neovascularization, Pathologic - genetics
Next-generation sequencing
Nucleotide sequencing
Patients
Proteins
Ribonuclease
Ribonucleic acid
RNA
RNA, Circular - genetics
RNA, Circular - metabolism
Signal Transduction - genetics
T Cell Transcription Factor 1 - genetics
T Cell Transcription Factor 1 - metabolism
Tumors
Tumour progression
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Title Circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer: involvement of miR-30c-5p/TCF7 axis
URI https://www.ncbi.nlm.nih.gov/pubmed/34172072
https://www.proquest.com/docview/2553227243
https://www.proquest.com/docview/2545596137
https://pubmed.ncbi.nlm.nih.gov/PMC8229759
https://doaj.org/article/8dfd9ece872d4308b8152a36847ba412
Volume 20
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