CircHIPK3 contributes to cisplatin resistance in gastric cancer by blocking autophagy‐dependent ferroptosis
CircHIPK3 contributes to cisplatin resistance in gastric cancer by blocking autophagy‐dependent ferroptosis
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DOI：
10.1002/jcp.31093
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发表时间：
2023-08
影响因子：
5.6
通讯作者：
Ziqi Shang;Zhengdong Luo;Yifeng Wang;Qi Liu;Yiwei Xin;Mengjiao Zhang;Xinyang Li;Shunjie Zeng-Shunjie
中科院分区：
文献类型：
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作者：
Ziqi Shang;Zhengdong Luo;Yifeng Wang;Qi Liu;Yiwei Xin;Mengjiao Zhang;Xinyang Li;Shunjie Zeng-Shunjie
顺铂是胃癌（GC）的一线化疗药物。然而，其疗效受到化疗耐药性的影响，导致GC患者预后不良。最近，有证据表明，环状RNA（circRNA）和自噬依赖性铁凋亡的失调在癌症耐药性中起着关键作用。在此，我们首次报道了circHIPK 3在GC顺铂耐药中起着至关重要的作用。CircHIPK 3通过靶向自噬和铁凋亡调节顺铂耐药性。简而言之，敲低circHIPK 3通过经由miR-508 - 3 p/Bcl-2/beclin 1/SLC 7A 11轴增强铁凋亡来降低GC细胞顺铂抗性。总之，我们的结果表明，铁凋亡是一个有前途的战略，以改善顺铂耐药性。重要的是，血清外泌体circHIPK 3也可以是评估GC中顺铂耐药性的非侵入性指标。
Cisplatin is the first‐line chemotherapy for gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which leads to poor prognosis in GC patients. Recently, evidence has revealed that circular RNAs (circRNAs) and dysregulation of autophagy‐dependent ferroptosis play critical roles in cancer chemoresistance. Herein, for the first time we report that circHIPK3 has a vital role in GC cisplatin resistance. CircHIPK3 regulated cisplatin resistance by targeting autophagy and ferroptosis. In brief, knockdown circHIPK3 decreased GC cell cisplatin resistance by enhancing ferroptosis via the miR‐508‐3p/Bcl‐2/beclin1/SLC7A11 axis. Taken together, our results demonstrate that ferroptosis is a promising strategy to ameliorate cisplatin resistance. Importantly, serum exosomal circHIPK3 could also be a noninvasive indicator to evaluate cisplatin resistance in GC.