PLEKHA8P1 promotes tumor progression and indicates poor prognosis of liver cancer

Jiyeon Lee, Ji Hyun Hwang, Harim Chun, Wonjin Woo, Sekyung Oh, Jungmin Choi, Lark Kyun Kim

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number7614
JournalInternational journal of molecular sciences
Volume22
Issue number14
DOIs
Publication statusPublished - 2021 Jul 2

Keywords

  • 5-fluorouracil
  • Chemoresistance
  • Hepatocellular carcinoma
  • Long non-coding RNA
  • PLEKHA8
  • PLEKHA8P1
  • Pseudogene

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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