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lncRNA H19 的调控增强了白藜芦醇抑制癌细胞增殖和迁移的作用，其机制与内质网应激有关。

Modulation of lncRNA H19 enhances resveratrol-inhibited cancer cell proliferation and migration by regulating endoplasmic reticulum stress.

机构信息

College of Life and Health Sciences, Northeastern University, Shenyang, China.

School of Computer Science and Software Engineering, University of Science and Technology Liaoning, Anshan, China.

出版信息

J Cell Mol Med. 2022 Apr;26(8):2205-2217. doi: 10.1111/jcmm.17242. Epub 2022 Feb 14.

DOI:10.1111/jcmm.17242
PMID:35166018
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8995452/
Abstract

The phytoalexin resveratrol exhibits anti-tumour activity in many types of cancer. In this study, we showed that resveratrol suppressed the survival of gastric tumour cells both in vivo and in vitro. Resveratrol promoted apoptosis, autophagy and endoplasmic reticulum (ER) stress in a dose-dependent manner. RNA-seq analysis showed that multiple cell death signalling pathways were activated after resveratrol treatment, while the use of ER stress activators (tunicamycin and thapsigargin) in combinatorial with resveratrol led to further inhibition of cancer cell survival. Results also showed that resveratrol altered the expression of several long non-coding RNAs (lncRNAs), including MEG3, PTTG3P, GAS5, BISPR, MALAT1 and H19. Knockdown of H19 in resveratrol-treated cells further enhanced the effects of resveratrol on apoptosis, ER stress and cell cycle S-phase arrest. Furthermore, the migratory ability of resveratrol-treated cells was dramatically decreased after H19 knockdown. In conclusion, resveratrol inhibited cancer cell survival, while knockdown of lncRNA H19 resulted in increased sensitivity to resveratrol therapy.

摘要

植物抗毒素白藜芦醇在多种癌症中具有抗肿瘤活性。在这项研究中，我们表明白藜芦醇在体内和体外均能抑制胃肿瘤细胞的存活。白藜芦醇以剂量依赖的方式促进细胞凋亡、自噬和内质网（ER）应激。RNA-seq 分析显示，白藜芦醇处理后多条细胞死亡信号通路被激活，而 ER 应激激活剂（衣霉素和 thapsigargin）与白藜芦醇联合使用可进一步抑制癌细胞的存活。结果还表明，白藜芦醇改变了几种长链非编码 RNA（lncRNA）的表达，包括 MEG3、PTTG3P、GAS5、BISPR、MALAT1 和 H19。在白藜芦醇处理的细胞中敲低 H19 进一步增强了白藜芦醇对细胞凋亡、ER 应激和细胞周期 S 期阻滞的影响。此外，敲低 H19 后，白藜芦醇处理的细胞迁移能力显著降低。总之，白藜芦醇抑制了癌细胞的存活，而敲低 lncRNA H19 导致对白藜芦醇治疗的敏感性增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/8995452/04993bd7c7a3/JCMM-26-2205-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/8995452/665e153ee335/JCMM-26-2205-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/8995452/b6df23fa2c1c/JCMM-26-2205-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/8995452/0a1d9ff93967/JCMM-26-2205-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/8995452/792ee1d9532d/JCMM-26-2205-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/8995452/56a9e01d8aaf/JCMM-26-2205-g003.jpg
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