线粒体核糖体蛋白L14通过调节甲状腺癌细胞内ROS水平促进细胞生长和侵袭。
Mitochondrial ribosomal protein L14 promotes cell growth and invasion through modulating ROS in thyroid cancer.
发表日期:2023 Feb 23
作者:
Hae Jong Kim, QuocKhanh Nguyen, Seung-Nam Jung, Mi Ae Lim, Chan Oh, Yudan Piao, YanLi Jin, Yea Eun Kang, Ju-Hui Kim, Young Il Kim, Jae Won Chang, Ho-Ryun Won, Bon Seok Koo
来源:
Clinical and Experimental Otorhinolaryngology
摘要:
Mitochondrial ribosomal protein L14 (MRPL14)由核基因编码,参与线粒体蛋白翻译。本研究旨在探讨MRPL14在甲状腺癌中的作用。我们利用癌症基因组图谱(TCGA)和忠南国立大学医院(CNUH)数据库研究MRPL14表达与临床病理特征的关系。我们在乳头状甲状腺癌(PTC)细胞系(B-CPAP和KTC-1)中进行了MRPL14的功能研究,包括增殖、迁移、侵袭、线粒体氧化磷酸化和反应性氧化物(ROS)生产。根据TCGA数据集,PTC组织失去了线粒体完整性,并显示与正常甲状腺组织相比整体线粒体核糖体蛋白(MRPs)的表达失调。在78个MRPs中,MRPL14在甲状腺癌组织中高度表达。MRPL14过表达与肿瘤进展、甲状腺外扩展和淋巴结转移显著相关。MRL14通过上皮-间充质转化相关蛋白促进甲状腺癌细胞的增殖和迁移。此外,MRPL14沉默可减少氧化磷酸化复合物IV(MTCO1)的表达并增加ROS的积累。与ROS清除剂联合治疗可恢复MRPL14沉默降低的细胞增殖和迁移,这表明ROS在MRPL14在甲状腺癌细胞中的致癌效应中起着重要的调节作用。我们的研究结果表明,MRPL14可能通过调控ROS促进甲状腺癌细胞的生长、迁移和侵袭。
The mitochondrial ribosomal protein L14 (MRPL14) is encoded by a nuclear gene and participates in mitochondrial protein translation. In this study, we aimed to investigate the role of MRPL14 in thyroid carcinoma.We investigated the association of expression of MRPL14 and clinicopathological features using the The Cancer Genome Atlas (TCGA) and Chungnam National University Hospital (CNUH) databases. Functional studies of MRPL14, including proliferation, migration, invasion, mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production, were performed in papillary thyroid carcinoma (PTC) cell lines (B-CPAP and KTC-1).Based on TCGA dataset, PTC tissues lost mitochondrial integrity and showed dysregulated expression of overall mitoribosomal proteins (MRPs) compared with normal thyroid tissues. Of 78 MRPs, MRPL14 was highly expressed in thyroid carcinoma tissues. MRPL14 overexpression was significantly associated with advanced tumor stage, extrathyroidal extension, and lymph node metastasis. MRL14 increased cell proliferation of thyroid cancer and promoted cell migration via epithelial-mesenchymal transition-related proteins. Moreover, MRPL14 knockdown reduced the expression of oxidative phosphorylation complex IV (MTCO1) and increased the accumulation of ROS. Co-treatment with a ROS scavenger restored cell proliferation and migration reduced by MRPL14 knockdown, which imply that ROS functions as a key regulator of the oncogenic effects of MRPL14 in thyroid cancer cells.Our findings indicate that MRPL14 may promote cell growth, migration, and invasion through modulating ROS in thyroid cancer cells.