Mitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1-miR-593-5p-MFF axis
Cisplatin 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2015 |
|---|---|
| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
|---|---|
| Enthalten in: |
Oncotarget - 6(2015), 17 vom: 20. Juni, Seite 14885-904 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Fan, Song [VerfasserIn] |
|---|
| Anmerkungen: |
Date Completed 18.04.2016 Date Revised 13.11.2018 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM248421980 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM248421980 | ||
| 003 | DE-627 | ||
| 005 | 20231224151351.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2015 xx |||||o 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0828.xml |
| 035 | |a (DE-627)NLM248421980 | ||
| 035 | |a (NLM)25912308 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Fan, Song |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1-miR-593-5p-MFF axis |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.04.2016 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Cisplatin 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BRCA1 | |
| 650 | 4 | |a MFF | |
| 650 | 4 | |a cisplatin sensitivity | |
| 650 | 4 | |a miR-593-5p | |
| 650 | 4 | |a mitochondrial fission | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a BRCA1 Protein |2 NLM | |
| 650 | 7 | |a BRCA1 protein, human |2 NLM | |
| 650 | 7 | |a MIRN593 microRNA, human |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Mff protein, human |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Mitochondrial Proteins |2 NLM | |
| 650 | 7 | |a Cisplatin |2 NLM | |
| 650 | 7 | |a Q20Q21Q62J |2 NLM | |
| 700 | 1 | |a Liu, Bodu |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Xiao-bin |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Zhaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Weixiong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Weiliang |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Qionglan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Youyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Yuxiong |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Shaowen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Daming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Jianglong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yilin |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Pu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Qixiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yinghua |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Pengnan |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Junjun |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Yuhuan |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Hongzhuang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Qihong |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Erwei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jinsong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Oncotarget |d 2010 |g 6(2015), 17 vom: 20. Juni, Seite 14885-904 |w (DE-627)NLM199620113 |x 1949-2553 |7 nnns |
| 773 | 1 | 8 | |g volume:6 |g year:2015 |g number:17 |g day:20 |g month:06 |g pages:14885-904 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 6 |j 2015 |e 17 |b 20 |c 06 |h 14885-904 | ||