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Conference Paper: Characterization of tumor-derived exosomes in BRCA-associated breast tumors

TitleCharacterization of tumor-derived exosomes in BRCA-associated breast tumors
Authors
Issue Date2018
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Proceedings of the 109th American Association for Cancer Research (AACR) Annual Meeting 2018, Chicago, IL, USA, 14-18 April 2018. In Cancer Research, 2018, v. 78 n. 13, Suppl, abstract no. 4415 How to Cite?
AbstractBackground: BRCA-mutated tumors are usually with higher grade than sporadic tumors and the biology is poorly understood. Exosomes are small membrane-derived vesicles that function to mediate cell-cell communication via the transfer of tumor-promoting microRNAs (miRNAs), RNAs and proteins. Interestingly, different spectrum of miRNAs is released by cancer cells to promote tumor growth and metastasis in breast cancer. However, the selectivity of miRNA released from tumor-derived exosomes and its relevance in cancer treatment has not been widely studied. Hence, this study is sought to characterize the role of exosomal-miRNA (exo-miR) for the development of BRCA-associated tumors. Methods: Plasma samples from patients with BRCA-positive and non-BRCA carriers were recruited and selected from the Hong Kong Hereditary Breast Cancer Family Registry. By using miRCURY LNA array, the exosomal-miRNA expressions in plasma of patient with BRCA-positive (n=4) and non-carriers (n=4), as well as healthy controls (n=4) were profiled. Selected miRNAs were further validated in pre- and post-operative plasma and paired primary tissues (n=40) using real-time RT-PCR. Functional study of miRNA was also carried out in the cell lines. Results: LNA array data showed that differential expressed BRCA-associated exo-miRNAs were identified. Upregulated miRs (miR-106a, miR-20a, miR-23a, miR-451 and miR-486) were validated in BRCA-positive, BRCA-negative and healthy controls by real-time RT-PCR. In addition, the expression levels of miR-106a, miR-451 and miR-486 were significantly lower in post-operative plasma of BRCA-carriers than non-carriers. Importantly, the expression of miR-451 was reduced after tumor resection in BRCA mutation carriers. In parallel, high expression of exo-miR-106a, miR-20a, miR-23a, miR-451 and miR-486 were also seen in breast cancer cell lines (MB-231 and MB-468) relative to normal breast cells (MCF-10A). We found that cells transfected with miR-451 inhibitor significantly reduce cell proliferation. Conclusions: These preliminary results reveal differential exo-miRNA profiles between BRCA carriers and non-carriers with breast cancer, and identify potential targets of dysregulated miRNAs which is crucial in disease progression of BRCA-associated breast cancers.
DescriptionSession PO.MCB10.06 - Noncoding RNAs: From Biology to Therapy - no. 4415/ 3
Persistent Identifierhttp://hdl.handle.net/10722/273098
ISSN
2017 Impact Factor: 9.13
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorShin, VY-
dc.contributor.authorSiu, JMT-
dc.contributor.authorCheuk, WYI-
dc.contributor.authorKwong, A-
dc.date.accessioned2019-08-06T09:22:29Z-
dc.date.available2019-08-06T09:22:29Z-
dc.date.issued2018-
dc.identifier.citationProceedings of the 109th American Association for Cancer Research (AACR) Annual Meeting 2018, Chicago, IL, USA, 14-18 April 2018. In Cancer Research, 2018, v. 78 n. 13, Suppl, abstract no. 4415-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/273098-
dc.descriptionSession PO.MCB10.06 - Noncoding RNAs: From Biology to Therapy - no. 4415/ 3-
dc.description.abstractBackground: BRCA-mutated tumors are usually with higher grade than sporadic tumors and the biology is poorly understood. Exosomes are small membrane-derived vesicles that function to mediate cell-cell communication via the transfer of tumor-promoting microRNAs (miRNAs), RNAs and proteins. Interestingly, different spectrum of miRNAs is released by cancer cells to promote tumor growth and metastasis in breast cancer. However, the selectivity of miRNA released from tumor-derived exosomes and its relevance in cancer treatment has not been widely studied. Hence, this study is sought to characterize the role of exosomal-miRNA (exo-miR) for the development of BRCA-associated tumors. Methods: Plasma samples from patients with BRCA-positive and non-BRCA carriers were recruited and selected from the Hong Kong Hereditary Breast Cancer Family Registry. By using miRCURY LNA array, the exosomal-miRNA expressions in plasma of patient with BRCA-positive (n=4) and non-carriers (n=4), as well as healthy controls (n=4) were profiled. Selected miRNAs were further validated in pre- and post-operative plasma and paired primary tissues (n=40) using real-time RT-PCR. Functional study of miRNA was also carried out in the cell lines. Results: LNA array data showed that differential expressed BRCA-associated exo-miRNAs were identified. Upregulated miRs (miR-106a, miR-20a, miR-23a, miR-451 and miR-486) were validated in BRCA-positive, BRCA-negative and healthy controls by real-time RT-PCR. In addition, the expression levels of miR-106a, miR-451 and miR-486 were significantly lower in post-operative plasma of BRCA-carriers than non-carriers. Importantly, the expression of miR-451 was reduced after tumor resection in BRCA mutation carriers. In parallel, high expression of exo-miR-106a, miR-20a, miR-23a, miR-451 and miR-486 were also seen in breast cancer cell lines (MB-231 and MB-468) relative to normal breast cells (MCF-10A). We found that cells transfected with miR-451 inhibitor significantly reduce cell proliferation. Conclusions: These preliminary results reveal differential exo-miRNA profiles between BRCA carriers and non-carriers with breast cancer, and identify potential targets of dysregulated miRNAs which is crucial in disease progression of BRCA-associated breast cancers.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.relation.ispartofAmerican Association for Cancer Research (AACR) Annual Meeting 2018-
dc.titleCharacterization of tumor-derived exosomes in BRCA-associated breast tumors-
dc.typeConference_Paper-
dc.identifier.emailShin, VY: vyshin@hku.hk-
dc.identifier.emailSiu, JMT: jensiu@hku.hk-
dc.identifier.emailCheuk, WYI: isacheuk@hku.hk-
dc.identifier.emailKwong, A: avakwong@hku.hk-
dc.identifier.authorityShin, VY=rp02000-
dc.identifier.authorityKwong, A=rp01734-
dc.identifier.doi10.1158/1538-7445.AM2018-4415-
dc.identifier.hkuros300917-
dc.identifier.volume78-
dc.identifier.issue13, Suppl-
dc.identifier.spageabstract no. 4415-
dc.identifier.epageabstract no. 4415-
dc.publisher.placeUnited States-

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