MiR-7-5p Is Involved in Ferroptosis Signaling and Radioresistance Thru the Generation of ROS in Radioresistant HeLa and SAS Cell Lines.
MiR-7-5p Is Involved in Ferroptosis Signaling and Radioresistance Thru the Generation of ROS in Radioresistant HeLa and SAS Cell Lines.
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DOI：
10.3390/ijms22158300
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发表时间：
2021-08-02
影响因子：
5.6
通讯作者：
Sato T
中科院分区：
文献类型：
--
作者：
Tomita K;Nagasawa T;Kuwahara Y;Torii S;Igarashi K;Roudkenar MH;Roushandeh AM;Kurimasa A;Sato T
在癌症治疗中，放射抗性或化学抗性细胞是主要问题。我们建立了临床相关的抗辐射（CRR）细胞，可以生存超过30天后，2戈伊/天的X射线照射。这些细胞还显示出对抗癌剂和过氧化氢（H2 O2）的抗性。我们之前已经证明，所有检查的CRR细胞都上调了miR-7- 5 p，并且在miR-7- 5 p敲低后，它们失去了辐射抗性。然而，放射抗性丧失的机制仍有待阐明。因此，我们通过使用CRR细胞敲低miR-7 - 5 p来研究miR-7 - 5 p在辐射抗性中的作用。因此，miR-7- 5 p的敲低增加了活性氧（ROS）、线粒体膜电位和细胞内Fe 2+量。此外，miR-7- 5 p敲低导致铁储存基因（如铁蛋白）表达下调，铁凋亡标志物ALOX 12基因表达上调，以及Liperfluo量增加。ALOX 12过表达后H2 O2处理导致细胞内H2 O2含量增加和脂质过氧化作用增强。相比之下，miR-7- 5 p敲低似乎不参与考克斯-2和糖酵解信号，但影响CRR细胞的形态。这些结果表明，miR-7- 5 p通过ROS产生控制辐射抗性，ROS产生导致铁凋亡。
In cancer therapy, radioresistance or chemoresistance cells are major problems. We established clinically relevant radioresistant (CRR) cells that can survive over 30 days after 2 Gy/day X-ray exposures. These cells also show resistance to anticancer agents and hydrogen peroxide (H2O2). We have previously demonstrated that all the CRR cells examined had up-regulated miR-7-5p and after miR-7-5p knockdown, they lost radioresistance. However, the mechanism of losing radioresistance remains to be elucidated. Therefore, we investigated the role of miR-7-5p in radioresistance by knockdown of miR-7-5p using CRR cells. As a result, knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+ amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount. H2O2 treatment after ALOX12 overexpression led to the enhancement of intracellular H2O2 amount and lipid peroxidation. By contrast, miR-7-5p knockdown seemed not to be involved in COX-2 and glycolysis signaling but affected the morphology of CRR cells. These results indicate that miR-7-5p control radioresistance via ROS generation that leads to ferroptosis.
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影响因子：
3.3
作者：
Liou GY;Storz P
通讯作者：
Storz P
影响因子：
8
作者：
Janakiraman H;House RP;Talwar S;Courtney SM;Hazard ES;Hardiman G;Mehrotra S;Howe PH;Gangaraju V;Palanisamy V
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影响因子：
64.5
作者：
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Stockwell BR
影响因子：
5.7
作者：
Kuwahara, Yoshikazu;Li, Li;Fukumoto, Manabu
通讯作者：
Fukumoto, Manabu
影响因子：
2
作者：
Kuwahara, Yoshikazu;Mori, Miyuki;Fukumoto, Manabu
通讯作者：
Fukumoto, Manabu