Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling.
Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling.
复制标题
沉默lncRNA MALAT1通过miR-145-5p/MUC1信号通路促进Erastin诱导的子宫内膜异位症铁下垂。
DOI：
10.1038/s41420-022-00975-w
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发表时间：
2022-04-11
影响因子：
7
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Liang Z;Wu Q;Wang H;Tan J;Wang H;Gou Y;Cao Y;Li Z;Zhang Z
子宫内膜异位症是一种慢性疾病，其特征是子宫内膜腺体和间质植入子宫外。然而，子宫内膜异位症的发病机制仍不清楚。迄今为止，由于存在各种副作用，还没有完全有效的无创伤治疗方法。最近的数据表明，铁死亡是一种新的公认的非凋亡调节的细胞死亡形式，其特征是铁依赖性和致命的脂质过氧化积累，在许多疾病的治疗中显示出巨大的前景。在本研究中，我们验证了erastin诱导异位子宫内膜基质细胞（EESC）的铁死亡。此外，我们发现在erastin诱导的铁死亡过程中，转移相关肺腺癌转录物1（MALAT1）的表达降低。在erastin处理后，MALAT1的敲低显着加剧了对细胞活力的抑制，并增加了EESC中细胞内铁、Liperfluo和MDA的水平。从机制上讲，我们证明 MALAT1 作为 miR-145-5p 的竞争性内源 RNA 来调节 MUC1（铁死亡的抑制因子）的表达。 MALAT1 敲低介导的铁死亡细胞死亡和 MUC1 下调可以通过抑制 miR-145-5p 来消除。此外，MUC1 敲低可以消除 miR-145-5p 抑制介导的铁死亡细胞死亡。此外，erastin诱导的铁死亡通过体内MALAT1/miR-145-5p/MUC1轴缩小子宫内膜异位病变。综上所述，我们的数据表明，MALAT1 的敲低通过 miR-145-5p/MUC1 信号传导促进erastin治疗后的铁死亡。 MALAT1 敲低和erastin 诱导对铁死亡的协同作用可能成为子宫内膜异位症的新治疗策略。
Endometriosis is a chronic disorder characterized by the implantation of endometrial glands and stroma outside the uterus. However, the pathogenesis of endometriosis is still unclear. To date, there is no fully effective treatment without trauma because of various side effects. Recent data suggest that ferroptosis is a novel recognized form of nonapoptosis-regulated cell death characterized by iron-dependent and lethal lipid peroxidation accumulation, showing great promise in the treatment of many diseases. In the present study, we verified that erastin induced ferroptosis in ectopic endometrial stromal cells (EESCs). Furthermore, we found that the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was decreased during erastin-induced ferroptosis. Knockdown of MALAT1 significantly aggravated the inhibition of cell viability and increased intracellular iron, Liperfluo, and MDA levels in EESCs upon erastin treatment. Mechanistically, we demonstrated that MALAT1 served as a competing endogenous RNA of miR-145-5p to regulate the expression of MUC1, a suppressor of ferroptosis. MALAT1 knockdown-mediated ferroptotic cell death and MUC1 downregulation could be abrogated by inhibition of miR-145-5p. In addition, miR-145-5p inhibition-mediated ferroptotic cell death could be abolished by MUC1 knockdown. Furthermore, erastin-induced ferroptosis shrunk endometriotic lesions via the MALAT1/miR-145-5p/MUC1 axis in vivo. Taken together, our data indicate that knockdown of MALAT1 facilitates ferroptosis upon erastin treatment via miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis.
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DOI：
10.1177/03000605211042975
发表时间：
2021-09
期刊：
The Journal of international medical research
影响因子：
--
作者：
Cui DJ;Chen C;Yuan WQ;Yang YH;Han L
通讯作者：
Han L
影响因子：
3.6
作者：
Cai LJ;Tu L;Huang XM;Huang J;Qiu N;Xie GH;Liao JX;Du W;Zhang YY;Tian JY
通讯作者：
Tian JY
LncRNA OIP5-AS1 通过 miR-128-3p/SLC7A11 信号传导抑制长期镉暴露的前列腺癌中的铁死亡。
影响因子：
6.8
作者：
Zhang, Yangyi;Guo, Shanqi;Jiang, Xingkang
通讯作者：
Jiang, Xingkang
DOI：
10.1016/j.bbrc.2013.10.053
发表时间：
2013-11-29
影响因子：
3.1
作者：
Wu, Huijuan;Xiao, ZhengHua;Hao, Quan
通讯作者：
Hao, Quan
影响因子：
6.1
作者：
Li, Yajie;Zeng, Xinliu;Gao, Ying
通讯作者：
Gao, Ying