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Article: CircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17

TitleCircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17
Authors
KeywordsColorectal carcinoma
circLONP2
Metastasismicro
RNA-17
Issue Date2020
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
Citation
Molecular Cancer, 2020, v. 19 n. 1, p. article no. 60 How to Cite?
AbstractBackground: Metastasis causes the vast majority of colorectal carcinoma (CRC)-related deaths. However, little is known about the specific traits and underlying mechanisms of metastasis-initiating cells in primary CRC. And whether or not circular RNAs (circRNAs) take part in this particular event remain not adequately stated yet. Methods: A screening method based on Transwell assay was first applied to build CRC subgroups with different metastatic potential. High throughput RNA sequencing was used to find out novel metastatic drivers in CRC metastasis-initiating step. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of circRNAs in CRC metastasis. Results: A circRNA consisting of exon 8–11 of LONP2, termed as circLONP2, was upregulated in metastasis-initiating CRC subgroups. Aberrant higher expression of circLONP2 was observed in primary CRC tissues with established metastasis, and along the invasive margin in metastatic site. High expression of circLONP2 predicted unfavorable overall survival. Functional studies revealed that circLONP2 could enhance the invasiveness of CRC cells in vitro, and targeting circLONP2 through anti-sense oligonucleotide (ASO) dramatically reduced the penetrance of metastasis to foreign organs in vivo. Mechanically, circLONP2 directly interacted with and promoted the processing of primary microRNA-17 (pri-miR-17), through recruiting DiGeorge syndrome critical region gene 8 (DGCR8) and Drosha complex in DDX1-dependent manner. Meanwhile, upregulated mature miR-17-5p could be assembled into exosomes and internalized by neighboring cells to enhance their aggressiveness. Conclusions: Our data indicate that circLONP2 acts as key metastasis-initiating molecule during CRC progression through modulating the intracellular maturation and intercellular transfer of miR-17, resulting in dissemination of metastasis-initiating ability in primary site and acceleration of metastasis formation in foreign organs. circLONP2 could serve as an effective prognostic predictor and/or novel anti-metastasis therapeutic target in CRC treatment.
Persistent Identifierhttp://hdl.handle.net/10722/284551
ISSN
2018 Impact Factor: 10.679
2015 SCImago Journal Rankings: 2.337
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorHan, K-
dc.contributor.authorWang, FW-
dc.contributor.authorCao, CH-
dc.contributor.authorLiang, H-
dc.contributor.authorChen, JW-
dc.contributor.authorChen, RX-
dc.contributor.authorFeng, ZH-
dc.contributor.authorLuo, J-
dc.contributor.authorJin, XH-
dc.contributor.authorDuan, JL-
dc.contributor.authorLi, SM-
dc.contributor.authorMa, NF-
dc.contributor.authorYun, JP-
dc.contributor.authorGuan, XY-
dc.contributor.authorPan, ZZ-
dc.contributor.authorLan, P-
dc.contributor.authorXu, RH-
dc.contributor.authorXie, D-
dc.date.accessioned2020-08-07T08:59:15Z-
dc.date.available2020-08-07T08:59:15Z-
dc.date.issued2020-
dc.identifier.citationMolecular Cancer, 2020, v. 19 n. 1, p. article no. 60-
dc.identifier.issn1476-4598-
dc.identifier.urihttp://hdl.handle.net/10722/284551-
dc.description.abstractBackground: Metastasis causes the vast majority of colorectal carcinoma (CRC)-related deaths. However, little is known about the specific traits and underlying mechanisms of metastasis-initiating cells in primary CRC. And whether or not circular RNAs (circRNAs) take part in this particular event remain not adequately stated yet. Methods: A screening method based on Transwell assay was first applied to build CRC subgroups with different metastatic potential. High throughput RNA sequencing was used to find out novel metastatic drivers in CRC metastasis-initiating step. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of circRNAs in CRC metastasis. Results: A circRNA consisting of exon 8–11 of LONP2, termed as circLONP2, was upregulated in metastasis-initiating CRC subgroups. Aberrant higher expression of circLONP2 was observed in primary CRC tissues with established metastasis, and along the invasive margin in metastatic site. High expression of circLONP2 predicted unfavorable overall survival. Functional studies revealed that circLONP2 could enhance the invasiveness of CRC cells in vitro, and targeting circLONP2 through anti-sense oligonucleotide (ASO) dramatically reduced the penetrance of metastasis to foreign organs in vivo. Mechanically, circLONP2 directly interacted with and promoted the processing of primary microRNA-17 (pri-miR-17), through recruiting DiGeorge syndrome critical region gene 8 (DGCR8) and Drosha complex in DDX1-dependent manner. Meanwhile, upregulated mature miR-17-5p could be assembled into exosomes and internalized by neighboring cells to enhance their aggressiveness. Conclusions: Our data indicate that circLONP2 acts as key metastasis-initiating molecule during CRC progression through modulating the intracellular maturation and intercellular transfer of miR-17, resulting in dissemination of metastasis-initiating ability in primary site and acceleration of metastasis formation in foreign organs. circLONP2 could serve as an effective prognostic predictor and/or novel anti-metastasis therapeutic target in CRC treatment.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com-
dc.relation.ispartofMolecular Cancer-
dc.rightsMolecular Cancer. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectColorectal carcinoma-
dc.subjectcircLONP2-
dc.subjectMetastasismicro-
dc.subjectRNA-17-
dc.titleCircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17-
dc.typeArticle-
dc.identifier.emailGuan, XY: xyguan@hku.hk-
dc.identifier.authorityGuan, XY=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s12943-020-01184-8-
dc.identifier.pmid32188489-
dc.identifier.pmcidPMC7079398-
dc.identifier.scopuseid_2-s2.0-85082056535-
dc.identifier.hkuros312313-
dc.identifier.volume19-
dc.identifier.issue1-
dc.identifier.spagearticle no. 60-
dc.identifier.epagearticle no. 60-
dc.publisher.placeUnited Kingdom-

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