Loss of oncogenic miR-155 in tumor cells promotes tumor growth by enhancing C/EBP-β-mediated MDSC infiltration

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dc.contributor.authorS Kim-
dc.contributor.authorJin Hoi Song-
dc.contributor.authorSeok Ho Kim-
dc.contributor.authorP Qu-
dc.contributor.authorB K Martin-
dc.contributor.authorW S Sehareen-
dc.contributor.authorD C Haines-
dc.contributor.authorP C Lin-
dc.contributor.authorS K Sharan-
dc.contributor.authorS Chang-
dc.date.accessioned2017-04-19T10:20:49Z-
dc.date.available2017-04-19T10:20:49Z-
dc.date.issued2016-
dc.identifier.issn1949-2553-
dc.identifier.uri10.18632/oncotarget.7150ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/13238-
dc.description.abstractThe oncogenic role of microRNA-155 (miR-155) in leukemia is well established but its role in other cancers, especially breast cancer, is gradually emerging. In this study we examined the effect of mir-155 loss in a well-characterized spontaneous breast cancer mouse model where Brca1 and Trp53 are deleted by K14-Cre. miR-155 is known to be up-regulated in BRCA1-deficient tumors. Surprisingly, complete loss of miR-155 (miR-155ko/ko) did not alter the tumor free survival of the mutant mice. However, we found increased infiltration of myeloid derived suppressor cells (MDSCs) in miR-155 deficient tumors. In addition, cytokine/chemokine array analysis revealed altered level of cytokines that are implicated in the recruitment of MDSCs. Mechanistically, we identified C/EBP-β, a known miR-155 target, to regulate the expression of these cytokines in the miR-155-deficient cells. Furthermore, using an allograft model, we showed that inhibition of miR-155 in cancer cells suppressed in vivo growth, which was restored by the loss of miR-155 in the microenvironment. Taken together, we have uncovered a novel tumor suppressive function of miR-155 in the tumor microenvironment, which is also dependent on miR-155 expression in the tumor cells. Because of the oncogenic as well as tumor suppressive roles of miR-155, our findings warrant caution against a systemic inhibition of miR-155 for anticancer therapy.-
dc.publisherImpact Journalsko
dc.titleLoss of oncogenic miR-155 in tumor cells promotes tumor growth by enhancing C/EBP-β-mediated MDSC infiltration-
dc.title.alternativeLoss of oncogenic miR-155 in tumor cells promotes tumor growth by enhancing C/EBP-β-mediated MDSC infiltration-
dc.typeArticle-
dc.citation.titleOncotarget-
dc.citation.number10-
dc.citation.endPage11112-
dc.citation.startPage11094-
dc.citation.volume7-
dc.contributor.affiliatedAuthorJin Hoi Song-
dc.contributor.affiliatedAuthorSeok Ho Kim-
dc.contributor.alternativeName김시내-
dc.contributor.alternativeName송진회-
dc.contributor.alternativeName김석호-
dc.contributor.alternativeNameQu-
dc.contributor.alternativeNameMartin-
dc.contributor.alternativeNameSehareen-
dc.contributor.alternativeNameHaines-
dc.contributor.alternativeNameLin-
dc.contributor.alternativeNameSharan-
dc.contributor.alternativeName장수환-
dc.identifier.bibliographicCitationOncotarget, vol. 7, no. 10, pp. 11094-11112-
dc.identifier.doi10.18632/oncotarget.7150-
dc.subject.keywordBreast cancer-
dc.subject.keywordC/EBP-beta-
dc.subject.keywordCytokine-
dc.subject.keywordMDSC-
dc.subject.keywordmiR-155-
dc.subject.localbreast cancer-
dc.subject.localBreast cancer-
dc.subject.localBreast Cancer-
dc.subject.localC/EBPβ-
dc.subject.localC/EBP-beta-
dc.subject.localcytokine-
dc.subject.localCytokines-
dc.subject.localCytokine-
dc.subject.localMDSC-
dc.subject.localmiR-155-
dc.description.journalClassN-
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