<i>PLEKHA8P1</i> Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer

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 regu...

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Main Authors: Jiyeon Lee, Ji-Hyun Hwang, Harim Chun, Wonjin Woo, Sekyung Oh, Jungmin Choi, Lark Kyun Kim
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/14/7614
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author Jiyeon Lee
Ji-Hyun Hwang
Harim Chun
Wonjin Woo
Sekyung Oh
Jungmin Choi
Lark Kyun Kim
author_facet Jiyeon Lee
Ji-Hyun Hwang
Harim Chun
Wonjin Woo
Sekyung Oh
Jungmin Choi
Lark Kyun Kim
author_sort Jiyeon Lee
collection DOAJ
description 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 (<i>PLEKHA8P1</i>) and its parental gene (<i>PLEKHA8</i>), 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 <i>PLEKHA8</i>, 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.
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spelling doaj.art-d0871ec42cff4b5382a077a5e52b48632023-11-22T04:01:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214761410.3390/ijms22147614<i>PLEKHA8P1</i> Promotes Tumor Progression and Indicates Poor Prognosis of Liver CancerJiyeon Lee0Ji-Hyun Hwang1Harim Chun2Wonjin Woo3Sekyung Oh4Jungmin Choi5Lark Kyun Kim6Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaInterdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University, Seoul 03722, KoreaDepartment of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, KoreaSeverance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaDepartment of Medical Science, Catholic Kwandong University College of Medicine, Incheon 22711, KoreaDepartment of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, KoreaSeverance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaHepatocellular 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 (<i>PLEKHA8P1</i>) and its parental gene (<i>PLEKHA8</i>), 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 <i>PLEKHA8</i>, 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.https://www.mdpi.com/1422-0067/22/14/7614pseudogenelong non-coding RNAhepatocellular carcinoma5-fluorouracilchemoresistance<i>PLEKHA8P1</i>
spellingShingle Jiyeon Lee
Ji-Hyun Hwang
Harim Chun
Wonjin Woo
Sekyung Oh
Jungmin Choi
Lark Kyun Kim
<i>PLEKHA8P1</i> Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer
International Journal of Molecular Sciences
pseudogene
long non-coding RNA
hepatocellular carcinoma
5-fluorouracil
chemoresistance
<i>PLEKHA8P1</i>
title <i>PLEKHA8P1</i> Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer
title_full <i>PLEKHA8P1</i> Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer
title_fullStr <i>PLEKHA8P1</i> Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer
title_full_unstemmed <i>PLEKHA8P1</i> Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer
title_short <i>PLEKHA8P1</i> Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer
title_sort i plekha8p1 i promotes tumor progression and indicates poor prognosis of liver cancer
topic pseudogene
long non-coding RNA
hepatocellular carcinoma
5-fluorouracil
chemoresistance
<i>PLEKHA8P1</i>
url https://www.mdpi.com/1422-0067/22/14/7614
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