Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis

Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But th...

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Published inTheranostics Vol. 10; no. 18; pp. 8211 - 8226
Main Authors Yang, Haiou, Zhang, Haiyang, Yang, Yuchong, Wang, Xinyi, Deng, Ting, Liu, Rui, Ning, Tao, Bai, Ming, Li, Hongli, Zhu, Kegan, Li, Jialu, Fan, Qian, Ying, Guoguang, Ba, Yi
Format Journal Article
LanguageEnglish
Published Australia Ivyspring International Publisher Pty Ltd 01.01.2020
Ivyspring International Publisher
Subjects
Animal research
Animals
Blood vessels
Cell culture
Cell Hypoxia - genetics
Cell Line, Tumor
Cell Movement - genetics
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Colorectal Neoplasms - surgery
Communication
Disease Progression
Epoxy resins
Exosomes - metabolism
Female
Gene Expression Regulation, Neoplastic
Hospitals
Humans
Hypoxia
Male
Medical prognosis
Metastasis
Mice
MicroRNAs
MicroRNAs - metabolism
Middle Aged
Phosphorylation
Proteins
Research Paper
Rho Guanine Nucleotide Exchange Factors - genetics
rhoA GTP-Binding Protein - genetics
RNA, Circular - metabolism
Signal Transduction - genetics
Transmission electron microscopy
United States > US
China
circRNAs
hypoxia
colorectal cancer
exosomes
cancer metastasis
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Abstract Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But the molecular mechanism remains poorly understood. Differential expression of circRNAs in plasma exosomes of CRC patients and normal subjects was performed by screening. Exosomes were isolated by ultra-centrifugation and RNA expressions were determined by RT-qPCR. The migratory capacity of cells was performed by high intension imaging, wound healing assay and transwell chamber migration assay. Circ-133 is enriched in the plasma exosomes of CRC patients and increased with the disease progression. Exosomal circ-133 derived from hypoxic cells delivered into normoxic cells and promoted cancer metastasis by acting on miR-133a/GEF-H1/RhoA axis. Meanwhile, animal experiments revealed that knockdown of circ-133 can inhibit tumor metastasis. Circ-133 is expected to be a new biomarker for monitoring tumor progression and might be a novel therapeutic target. Hypoxia-derived exosomal circ-133 transported into normaxic cancer cells and promoted cell migration via miR-133a/GEF-H1/RhoA axis. This study reveals a potential mechanism for that the intra-tumor heterogeneity of oxygen promote cancer progression.
AbstractList Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But the molecular mechanism remains poorly understood. Methods: Differential expression of circRNAs in plasma exosomes of CRC patients and normal subjects was performed by screening. Exosomes were isolated by ultra-centrifugation and RNA expressions were determined by RT-qPCR. The migratory capacity of cells was performed by high intension imaging, wound healing assay and transwell chamber migration assay. Results: Circ-133 is enriched in the plasma exosomes of CRC patients and increased with the disease progression. Exosomal circ-133 derived from hypoxic cells delivered into normoxic cells and promoted cancer metastasis by acting on miR-133a/GEF-H1/RhoA axis. Meanwhile, animal experiments revealed that knockdown of circ-133 can inhibit tumor metastasis. Circ-133 is expected to be a new biomarker for monitoring tumor progression and might be a novel therapeutic target. Conclusions: Hypoxia-derived exosomal circ-133 transported into normaxic cancer cells and promoted cell migration via miR-133a/GEF-H1/RhoA axis. This study reveals a potential mechanism for that the intra-tumor heterogeneity of oxygen promote cancer progression.
Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But the molecular mechanism remains poorly understood. Methods: Differential expression of circRNAs in plasma exosomes of CRC patients and normal subjects was performed by screening. Exosomes were isolated by ultra-centrifugation and RNA expressions were determined by RT-qPCR. The migratory capacity of cells was performed by high intension imaging, wound healing assay and transwell chamber migration assay. Results: Circ-133 is enriched in the plasma exosomes of CRC patients and increased with the disease progression. Exosomal circ-133 derived from hypoxic cells delivered into normoxic cells and promoted cancer metastasis by acting on miR-133a/GEF-H1/RhoA axis. Meanwhile, animal experiments revealed that knockdown of circ-133 can inhibit tumor metastasis. Circ-133 is expected to be a new biomarker for monitoring tumor progression and might be a novel therapeutic target. Conclusions: Hypoxia-derived exosomal circ-133 transported into normaxic cancer cells and promoted cell migration via miR-133a/GEF-H1/RhoA axis. This study reveals a potential mechanism for that the intra-tumor heterogeneity of oxygen promote cancer progression.Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But the molecular mechanism remains poorly understood. Methods: Differential expression of circRNAs in plasma exosomes of CRC patients and normal subjects was performed by screening. Exosomes were isolated by ultra-centrifugation and RNA expressions were determined by RT-qPCR. The migratory capacity of cells was performed by high intension imaging, wound healing assay and transwell chamber migration assay. Results: Circ-133 is enriched in the plasma exosomes of CRC patients and increased with the disease progression. Exosomal circ-133 derived from hypoxic cells delivered into normoxic cells and promoted cancer metastasis by acting on miR-133a/GEF-H1/RhoA axis. Meanwhile, animal experiments revealed that knockdown of circ-133 can inhibit tumor metastasis. Circ-133 is expected to be a new biomarker for monitoring tumor progression and might be a novel therapeutic target. Conclusions: Hypoxia-derived exosomal circ-133 transported into normaxic cancer cells and promoted cell migration via miR-133a/GEF-H1/RhoA axis. This study reveals a potential mechanism for that the intra-tumor heterogeneity of oxygen promote cancer progression.
Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But the molecular mechanism remains poorly understood. Methods: Differential expression of circRNAs in plasma exosomes of CRC patients and normal subjects was performed by screening. Exosomes were isolated by ultra-centrifugation and RNA expressions were determined by RT-qPCR. The migratory capacity of cells was performed by high intension imaging, wound healing assay and transwell chamber migration assay. Results: Circ-133 is enriched in the plasma exosomes of CRC patients and increased with the disease progression. Exosomal circ-133 derived from hypoxic cells delivered into normoxic cells and promoted cancer metastasis by acting on miR-133a/GEF-H1/RhoA axis. Meanwhile, animal experiments revealed that knockdown of circ-133 can inhibit tumor metastasis. Circ-133 is expected to be a new biomarker for monitoring tumor progression and might be a novel therapeutic target. Conclusions: Hypoxia-derived exosomal circ-133 transported into normaxic cancer cells and promoted cell migration via miR-133a/GEF-H1/RhoA axis. This study reveals a potential mechanism for that the intra-tumor heterogeneity of oxygen promote cancer progression.
Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But the molecular mechanism remains poorly understood. Differential expression of circRNAs in plasma exosomes of CRC patients and normal subjects was performed by screening. Exosomes were isolated by ultra-centrifugation and RNA expressions were determined by RT-qPCR. The migratory capacity of cells was performed by high intension imaging, wound healing assay and transwell chamber migration assay. Circ-133 is enriched in the plasma exosomes of CRC patients and increased with the disease progression. Exosomal circ-133 derived from hypoxic cells delivered into normoxic cells and promoted cancer metastasis by acting on miR-133a/GEF-H1/RhoA axis. Meanwhile, animal experiments revealed that knockdown of circ-133 can inhibit tumor metastasis. Circ-133 is expected to be a new biomarker for monitoring tumor progression and might be a novel therapeutic target. Hypoxia-derived exosomal circ-133 transported into normaxic cancer cells and promoted cell migration via miR-133a/GEF-H1/RhoA axis. This study reveals a potential mechanism for that the intra-tumor heterogeneity of oxygen promote cancer progression.
Author Li, Jialu
Li, Hongli
Ba, Yi
Yang, Haiou
Liu, Rui
Wang, Xinyi
Bai, Ming
Zhang, Haiyang
Deng, Ting
Fan, Qian
Zhu, Kegan
Ning, Tao
Yang, Yuchong
Ying, Guoguang
AuthorAffiliation 3 Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, China
1 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
2 Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, China
AuthorAffiliation_xml – name: 1 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
– name: 3 Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, China
– name: 2 Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, China
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/32724467$$D View this record in MEDLINE/PubMed
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Issue 18
Keywords circRNAs
hypoxia
colorectal cancer
exosomes
cancer metastasis
Language English
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PublicationTitle Theranostics
PublicationTitleAlternate Theranostics
PublicationYear 2020
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References 35401824 - Theranostics. 2022 Mar 6;12(6):2635-2636. doi: 10.7150/thno.71495
38855172 - Theranostics. 2024 May 18;14(8):3081. doi: 10.7150/thno.98415
References_xml – reference: 35401824 - Theranostics. 2022 Mar 6;12(6):2635-2636. doi: 10.7150/thno.71495
– reference: 38855172 - Theranostics. 2024 May 18;14(8):3081. doi: 10.7150/thno.98415
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Snippet Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the...
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StartPage 8211
SubjectTerms Animal research
Animals
Blood vessels
Cell culture
Cell Hypoxia - genetics
Cell Line, Tumor
Cell Movement - genetics
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Colorectal Neoplasms - surgery
Communication
Disease Progression
Epoxy resins
Exosomes - metabolism
Female
Gene Expression Regulation, Neoplastic
Hospitals
Humans
Hypoxia
Male
Medical prognosis
Metastasis
Mice
MicroRNAs
MicroRNAs - metabolism
Middle Aged
Phosphorylation
Proteins
Research Paper
Rho Guanine Nucleotide Exchange Factors - genetics
rhoA GTP-Binding Protein - genetics
RNA, Circular - metabolism
Signal Transduction - genetics
Transmission electron microscopy
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Title Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis
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