METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy
METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy
复制标题
METase/lncRNA HULC/FoxM1 通过抑制自噬降低胃癌顺铂耐药性
DOI：
10.1007/s00432-019-03015-w
复制
发表时间：
2019-10-01
影响因子：
3.6
通讯作者：
Liu, Chuan
中科院分区：
文献类型：
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作者：
Xin, Lin;Zhou, Qi;Liu, Chuan
背景自噬在调节胃癌细胞对顺铂(CDDP)的耐药性中起着重要作用。然而，甲硫氨酸酶(METase)调控胃癌细胞自噬和顺铂耐药的机制尚不清楚。材料与方法用Western印迹法检测自噬相关蛋白、多药耐药基因1(MDR-1)和FOXM1蛋白的表达。用qRT-PCR方法检测LncRNA HULC。CCK-8比色法检测细胞存活率。通过RNA下拉和RIP实验证实了lncRNA HULC与FOXM1的相互作用。结果携带METase的慢病毒载体(LV-METase)可抑制耐药胃癌细胞的自噬和顺铂耐药。转染LV-METase的耐药胃癌细胞中，LncRNA HULC的表达显著下调。此外，我们还发现lncRNA HULC与FOXM1相互作用。此外，METase通过调节HULC/FOXM1抑制自噬降低耐药细胞对顺铂的耐药性，干扰HULC抑制自噬通过调节FOXM1降低耐药细胞对顺铂的耐药性。最后，干扰HULC抑制了体内肿瘤的生长。结论METase通过调节HULC/FOXM1通路抑制自噬，从而降低耐药胃癌细胞对顺铂的耐药性。
Background Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of autophagy and CDDP resistance of gastric cancer cells is still not clear. Materials and methods Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay. Results Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo. Conclusion METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.