Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon, Ehime, 791-0295, Japan.
Sci Rep. 2021 Apr 12;11(1):7926. doi: 10.1038/s41598-021-86592-6.
Endoplasmic reticulum (ER) stress plays an important role in hepatocyte degeneration, especially in patients with chronic liver injury. Protein kinase R-like endoplasmic reticulum kinase (PERK) is a key molecule in ER stress. PERK may contribute to apoptotic cell death in HCC, however the details of the mechanism are not clear. In this study, we identified PERK-associated molecules using transcriptome analysis. We modulated PERK expression using a plasmid, tunicamycin and siRNA against PERK, and then confirmed the target gene expression with real-time PCR and Northern blotting. We further analyzed the apoptotic function. Transcriptome analysis revealed that expression of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), which is a long noncoding RNA, was strongly correlated with the function of PERK. The expression of RMRP was correlated with the expression of PERK in experiments with the siRNA and PERK plasmid in both HCC cell lines and human HCC tissue. Furthermore, RMRP downregulation induced apoptotic cell death. RMRP is downregulated by PERK, which induces apoptosis in HCC. RMRP could be a new therapeutic target to regulate HCC in patients with chronic liver diseases associated with ER stress.
内质网（ER）应激在肝细胞变性中起重要作用，特别是在慢性肝损伤患者中。蛋白激酶 R 样内质网激酶（PERK）是 ER 应激中的关键分子。PERK 可能导致 HCC 中的凋亡细胞死亡，但机制细节尚不清楚。在这项研究中，我们使用转录组分析鉴定了 PERK 相关分子。我们使用质粒、衣霉素和 PERK 的 siRNA 调节 PERK 的表达，然后使用实时 PCR 和 Northern 印迹法确认靶基因的表达。我们进一步分析了凋亡功能。转录组分析表明，线粒体 RNA 加工内切核糖核酸酶（RMRP）的 RNA 成分的表达与 PERK 的功能强烈相关，该 RNA 成分是一种长非编码 RNA。在 HCC 细胞系和人 HCC 组织中使用 siRNA 和 PERK 质粒的实验中，RMRP 的表达与 PERK 的表达相关。此外，RMRP 的下调诱导了凋亡细胞死亡。PERK 下调 RMRP，诱导 HCC 中的细胞凋亡。RMRP 可能成为一种新的治疗靶点，用于调节与 ER 应激相关的慢性肝病患者的 HCC。
