LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling
LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling
复制标题
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。
DOI：
10.1016/j.ecoenv.2021.112376
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发表时间：
2021-05-26
影响因子：
6.8
通讯作者：
Jiang, Xingkang
中科院分区：
文献类型：
--
作者：
Zhang, Yangyi;Guo, Shanqi;Jiang, Xingkang
以往的研究表明，镉（Cd）是前列腺癌（PCa）的致病因素之一，但慢性Cd暴露对前列腺癌进展的影响尚不清楚。此外，长链非编码rna （long noncoding RNAs, lncRNAs）是否参与了PCa长时间暴露于Cd的调控还有待阐明。在本研究中，我们发现前列腺癌患者血清Cd浓度与Gleason评分和肿瘤-淋巴结-转移（TNM）分级呈正相关。为了模拟前列腺癌慢性Cd暴露，我们将PC3和DU145细胞置于长期低剂量Cd暴露下，并进一步研究肿瘤行为。功能研究发现，慢性镉暴露在体外和体内促进细胞生长和铁下垂抵抗。此外，我们发现慢性Cd暴露后，PC3和DU145细胞中lncRNA OIP5-AS1的表达显著升高。OIP5-AS1表达失调介导细胞生长和cd诱导的铁下垂。在机制上，我们证明了OIP5-AS1作为miR-128-3p的内源性海绵来调节SLC7A11的表达，SLC7A11是铁下垂的替代标志物。此外，miR-128-3p通过增强铁下垂来降低细胞活力。综上所述，我们的数据表明，lncRNA OIP5-AS1通过miR-128-3p/SLC7A11信号传导促进PCa的进展和铁沉耐药性。
Previous studies suggest that cadmium (Cd) is one of the causative factors of prostate cancer (PCa), but the effect of chronic Cd exposure on PCa progression remains unclear. Besides, whether long noncoding RNAs (lncRNAs) are involved in the regulation of prolonged exposure to Cd in PCa needs to be elucidated. In the present study, we found that the serum concentration of Cd in PCa patients was positively correlated with the Gleason score and tumor-node-metastasis (TNM) classification. To simulate chronic Cd exposure in PCa, we subjected PC3 and DU145 cells to long-term, low-dose Cd exposure and further examined tumor behavior. Functional studies identified that chronic Cd exposure promoted cell growth and ferroptosis resistance in vitro and in vivo. Furthermore, we found that lncRNA OIP5-AS1 expression was greatly elevated in PC3 and DU145 cells upon chronic Cd exposure. Dysregulation of OIP5-AS1 expression mediated cell growth and Cd-induced ferroptosis. Mechanistically, we demonstrated that OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, our data indicate that lncRNA OIP5-AS1 promotes PCa progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling.