<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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MDPI AG
2021-07-01
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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. |
first_indexed | 2024-03-10T09:36:41Z |
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institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T09:36:41Z |
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series | International Journal of Molecular Sciences |
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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