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Article: Mitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1-miR-593-5p-MFF axis

TitleMitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1-miR-593-5p-MFF axis
Authors
Issue Date2015
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2015, v. 6 n. 17, p. 14885-14904 How to Cite?
AbstractCisplatin has been widely employed as a cornerstone chemotherapy treatment for a wide spectrum of solid neoplasms; increasing tumor responsiveness to cisplatin has been a topic of interest for the past 30 years. Strong evidence has indicated that mitochondrial fission participates in the regulation of apoptosis in many diseases; however, whether mitochondrial fission regulates cisplatin sensitivity remains poorly understood. Here, we show that MFF mediated mitochondrial fission and apoptosis in tongue squamous cell carcinoma (TSCC) cells after cisplatin treatment and that miR-593-5p was downregulated in this process. miR-593-5p attenuated mitochondrial fission and cisplatin sensitivity by targeting the 3’ untranslated region sequence of MFF and inhibiting its translation. In exploring the underlying mechanism of miR-593-5p downregulation, we observed that BRCA1 transactivated miR-593-5p expression and attenuated cisplatin sensitivity in vitro. The BRCA1-miR-593-5p-MFF axis also affected cisplatin sensitivity in vivo. Importantly, in a retrospective analysis of multiple centers, we further found that the BRCA1-miR-593-5p-MFF axis was significantly associated with cisplatin sensitivity and the survival of patients with TSCC. Together, our data reveal a model for mitochondrial fission regulation at the transcriptional and post-transcriptional levels; we also reveal a new pathway for BRCA1 in determining cisplatin sensitivity through the mitochondrial fission program.
Persistent Identifierhttp://hdl.handle.net/10722/211689
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294

 

DC FieldValueLanguage
dc.contributor.authorFan, S-
dc.contributor.authorLiu, B-
dc.contributor.authorSun, L-
dc.contributor.authorLv, XB-
dc.contributor.authorLin, Z-
dc.contributor.authorChen, W-
dc.contributor.authorTang, Q-
dc.contributor.authorWang, Y-
dc.contributor.authorSu, Y-
dc.contributor.authorJin, S-
dc.contributor.authorZhang, D-
dc.contributor.authorZhong, J-
dc.contributor.authorLi, Y-
dc.contributor.authorWen, B-
dc.contributor.authorZhang, Z-
dc.contributor.authorYang, P-
dc.contributor.authorZhou, B-
dc.contributor.authorLiang, Q-
dc.contributor.authorYu, X-
dc.contributor.authorZhu, Y-
dc.contributor.authorHu, P-
dc.contributor.authorChu, J-
dc.contributor.authorHuang, W-
dc.contributor.authorFeng, Y-
dc.contributor.authorPeng, H-
dc.contributor.authorHuang, Q-
dc.contributor.authorSong, E-
dc.contributor.authorLi, J-
dc.date.accessioned2015-07-21T02:07:59Z-
dc.date.available2015-07-21T02:07:59Z-
dc.date.issued2015-
dc.identifier.citationOncotarget, 2015, v. 6 n. 17, p. 14885-14904-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/211689-
dc.description.abstractCisplatin has been widely employed as a cornerstone chemotherapy treatment for a wide spectrum of solid neoplasms; increasing tumor responsiveness to cisplatin has been a topic of interest for the past 30 years. Strong evidence has indicated that mitochondrial fission participates in the regulation of apoptosis in many diseases; however, whether mitochondrial fission regulates cisplatin sensitivity remains poorly understood. Here, we show that MFF mediated mitochondrial fission and apoptosis in tongue squamous cell carcinoma (TSCC) cells after cisplatin treatment and that miR-593-5p was downregulated in this process. miR-593-5p attenuated mitochondrial fission and cisplatin sensitivity by targeting the 3’ untranslated region sequence of MFF and inhibiting its translation. In exploring the underlying mechanism of miR-593-5p downregulation, we observed that BRCA1 transactivated miR-593-5p expression and attenuated cisplatin sensitivity in vitro. The BRCA1-miR-593-5p-MFF axis also affected cisplatin sensitivity in vivo. Importantly, in a retrospective analysis of multiple centers, we further found that the BRCA1-miR-593-5p-MFF axis was significantly associated with cisplatin sensitivity and the survival of patients with TSCC. Together, our data reveal a model for mitochondrial fission regulation at the transcriptional and post-transcriptional levels; we also reveal a new pathway for BRCA1 in determining cisplatin sensitivity through the mitochondrial fission program.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleMitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1-miR-593-5p-MFF axis-
dc.typeArticle-
dc.identifier.emailSu, Y: richsu@hku.hk-
dc.identifier.authoritySu, Y=rp01916-
dc.description.naturepublished_or_final_version-
dc.identifier.pmid25912308-
dc.identifier.hkuros245348-
dc.identifier.volume6-
dc.identifier.issue17-
dc.identifier.spage14885-
dc.identifier.epage14904-
dc.publisher.placeUnited States-

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