Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea.
Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University, Seoul 03722, Korea.
Int J Mol Sci. 2021 Jul 16;22(14):7614. doi: 10.3390/ijms22147614.
Hepatocellular carcinoma (HCC) records the second-lowest 5-year survival rate despite the avalanche of research into diagnosis and therapy. One of the major obstacles in treatment is chemoresistance to drugs such as 5-fluorouracil (5-FU), making identification and elucidation of chemoresistance regulators highly valuable. As the regulatory landscape grows to encompass non-coding genes such as long non-coding RNAs (lncRNAs), a relatively new class of lncRNA has emerged in the form of pseudogene-derived lncRNAs. Through bioinformatics analyses of the TCGA LIHC dataset, we have systematically identified pseudogenes of prognostic value. Initial experimental validation of selected pseudogene-derived lncRNA () and its parental gene (), a well-studied transport protein in Golgi complex recently implicated as an oncogene in both colorectal and liver cancer, indicates that the pseudogene/parental gene pair promotes tumor progression and that their dysregulated expression levels affect 5-FU-induced chemoresistance in human HCC cell line FT3-7. Our study has thus confirmed cancer-related functions of , and laid the groundwork for identification and validation of oncogenic pseudogene-derived lncRNA that shows potential as a novel therapeutic target in circumventing chemoresistance induced by 5-FU.
肝细胞癌 (HCC) 的 5 年生存率虽然在诊断和治疗方面的研究如雨后春笋般涌现，但仍然是最低的。治疗的主要障碍之一是对药物如 5-氟尿嘧啶 (5-FU) 的化学耐药性，因此，鉴定和阐明化学耐药性调节剂具有很高的价值。随着调控领域的发展，涵盖了非编码基因如长非编码 RNA (lncRNA)，一种相对较新的 lncRNA 形式——假基因衍生的 lncRNA 出现了。通过对 TCGA LIHC 数据集的生物信息学分析，我们系统地鉴定了具有预后价值的假基因。对选定的假基因衍生 lncRNA () 和其亲本基因 () 的初步实验验证，该基因是高尔基复合体中研究得很好的转运蛋白，最近被认为是结直肠癌和肝癌的致癌基因，表明假基因/亲本基因对促进肿瘤进展，其失调表达水平影响人 HCC 细胞系 FT3-7 中 5-FU 诱导的化学耐药性。因此，我们的研究证实了 的癌症相关功能，并为鉴定和验证具有潜在作为克服 5-FU 诱导的化学耐药性的新型治疗靶点的致癌性假基因衍生 lncRNA 奠定了基础。
