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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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.7150/thno.44419 |
| format | Article |
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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.</description><identifier>ISSN: 1838-7640</identifier><identifier>EISSN: 1838-7640</identifier><identifier>DOI: 10.7150/thno.44419</identifier><identifier>PMID: 32724467</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher Pty Ltd</publisher><subject>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</subject><ispartof>Theranostics, 2020-01, Vol.10 (18), p.8211-8226</ispartof><rights>The author(s).</rights><rights>2020. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-2f335c25a35e26b7d38e5af09ffa2b9ae922473a31cbdd442a46800d33f1f1eb3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381736/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381736/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32724467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Haiou</creatorcontrib><creatorcontrib>Zhang, Haiyang</creatorcontrib><creatorcontrib>Yang, Yuchong</creatorcontrib><creatorcontrib>Wang, Xinyi</creatorcontrib><creatorcontrib>Deng, Ting</creatorcontrib><creatorcontrib>Liu, Rui</creatorcontrib><creatorcontrib>Ning, Tao</creatorcontrib><creatorcontrib>Bai, Ming</creatorcontrib><creatorcontrib>Li, Hongli</creatorcontrib><creatorcontrib>Zhu, Kegan</creatorcontrib><creatorcontrib>Li, Jialu</creatorcontrib><creatorcontrib>Fan, Qian</creatorcontrib><creatorcontrib>Ying, Guoguang</creatorcontrib><creatorcontrib>Ba, Yi</creatorcontrib><title>Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis</title><title>Theranostics</title><addtitle>Theranostics</addtitle><description>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.</description><subject>Animal research</subject><subject>Animals</subject><subject>Blood vessels</subject><subject>Cell culture</subject><subject>Cell Hypoxia - genetics</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - surgery</subject><subject>Communication</subject><subject>Disease Progression</subject><subject>Epoxy resins</subject><subject>Exosomes - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Mice</subject><subject>MicroRNAs</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Research Paper</subject><subject>Rho Guanine Nucleotide Exchange Factors - genetics</subject><subject>rhoA GTP-Binding Protein - genetics</subject><subject>RNA, Circular - metabolism</subject><subject>Signal Transduction - genetics</subject><subject>Transmission electron microscopy</subject><issn>1838-7640</issn><issn>1838-7640</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdkd1q3DAQhUVpaUKamz5AEfSmFJzoz5Z9U1iWJFsILYT2Wozl0a6CbW0lOWzevkqThrTDwAzMx-EMh5D3nJ1pXrPzvJvDmVKKd6_IMW9lW-lGsdcv9iNymtItK6WY6Hj3lhxJoYVSjT4mu839Phw8UD8Pi8WB4iGkMMFIrY_25tuK7mOYQsZEJ8yQSvtEg6PrMIaINhdyDbPFSO-KSoa4xeznLb26uKw2_PxmF1YUDj69I28cjAlPn-YJ-Xl58WO9qa6_X31dr64rq7TIlXBS1lbUIGsUTa8H2WINjnXOgeg7wE4IpSVIbvthUEqAalrGBikddxx7eUK-POrul37CweKcI4xmH_0E8d4E8Obfy-x3ZhvujJYt17IpAp-eBGL4tWDKZvLJ4jjCjGFJRijRKt4KrQr68T_0NixxLu8ZUXdtMSo6XajPj5SNIaWI7tkMZ-YhQ_OQofmTYYE_vLT_jP5NTP4GAIuYag</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Yang, Haiou</creator><creator>Zhang, Haiyang</creator><creator>Yang, Yuchong</creator><creator>Wang, Xinyi</creator><creator>Deng, Ting</creator><creator>Liu, Rui</creator><creator>Ning, Tao</creator><creator>Bai, Ming</creator><creator>Li, Hongli</creator><creator>Zhu, Kegan</creator><creator>Li, Jialu</creator><creator>Fan, Qian</creator><creator>Ying, Guoguang</creator><creator>Ba, Yi</creator><general>Ivyspring International Publisher Pty Ltd</general><general>Ivyspring International Publisher</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200101</creationdate><title>Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis</title><author>Yang, Haiou ; 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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.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>32724467</pmid><doi>10.7150/thno.44419</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis |
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