PLEKHA8P1 Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer

International Journal of Molecular Sciences

Harim Chun¹  Jungmin Choi¹  Sekyung Oh²  Ji-Hyun Hwang³  Jiyeon Lee⁴  Lark Kyun Kim⁴  Wonjin Woo⁴ 

[1] Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Korea;Department of Medical Science, Catholic Kwandong University College of Medicine, Incheon 22711, Korea;Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University, Seoul 03722, Korea;Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea;

关键词: pseudogene;    long non-coding RNA;    hepatocellular carcinoma;    5-fluorouracil;    chemoresistance;    PLEKHA8P1;   

DOI  :  10.3390/ijms22147614

来源: DOAJ

【 摘 要 】

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 (PLEKHA8P1) and its parental gene (PLEKHA8), 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 PLEKHA8, 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.

【 授权许可】

Unknown