Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung Adenocarcinoma

The prognosis of patients with metastatic lung adenocarcinoma (LUAD) is poor. Although novel lung cancer treatments have been developed for metastatic LUAD, not all patients are fit to receive these treatments. The present study aimed to identify the novel regulatory genes in metastatic LUAD. Becaus...

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Main Authors: Meng-Chi Yen, Kuan-Li Wu, Yu-Wei Liu, Yung-Yun Chang, Chao-Yuan Chang, Jen-Yu Hung, Ying-Ming Tsai, Ya-Ling Hsu
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/10/5/378
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author Meng-Chi Yen
Kuan-Li Wu
Yu-Wei Liu
Yung-Yun Chang
Chao-Yuan Chang
Jen-Yu Hung
Ying-Ming Tsai
Ya-Ling Hsu
author_facet Meng-Chi Yen
Kuan-Li Wu
Yu-Wei Liu
Yung-Yun Chang
Chao-Yuan Chang
Jen-Yu Hung
Ying-Ming Tsai
Ya-Ling Hsu
author_sort Meng-Chi Yen
collection DOAJ
description The prognosis of patients with metastatic lung adenocarcinoma (LUAD) is poor. Although novel lung cancer treatments have been developed for metastatic LUAD, not all patients are fit to receive these treatments. The present study aimed to identify the novel regulatory genes in metastatic LUAD. Because the pleural cavity is a frequent metastasis site of LUAD, the adjacent non-tumor tissue, primary tumor tissue, and metastatic lung tumor tissue in the pleura of a single patient with LUAD were collected. The gene expression profiles of the collected samples were further analyzed via RNA sequencing and bioinformatic analysis. A high expression level of ubiquitin conjugating enzyme E2 H (UBE2H), a hypoxia-mediated gene, was identified in the metastatic malignant pleural tumor. After accessing the survival data in patients with lung adenocarcinoma through online databases, a high UBE2H expression was associated with poor survival for LUAD. UBE2H knockdown in two lung adenocarcinoma cell lines suppressed the cell migration capacity and reversed the epithelial–mesenchymal transition (EMT) signaling pathway. A high expression of UBE2H-targeting microRNAs, including miR-101, miR-30a, miR-30b, miR-328, and miR-497, were associated with a favorable prognosis. Moreover, the UBE2H expression revealed a significant correlation with the copy number variation. Taken together, the presence of UBE2H regulated the EMT program and metastasis in LUAD.
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spelling doaj.art-ae9e193bb4ff4168a98caed8999bc47f2023-11-21T17:30:21ZengMDPI AGBiology2079-77372021-04-0110537810.3390/biology10050378Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung AdenocarcinomaMeng-Chi Yen0Kuan-Li Wu1Yu-Wei Liu2Yung-Yun Chang3Chao-Yuan Chang4Jen-Yu Hung5Ying-Ming Tsai6Ya-Ling Hsu7Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanThe prognosis of patients with metastatic lung adenocarcinoma (LUAD) is poor. Although novel lung cancer treatments have been developed for metastatic LUAD, not all patients are fit to receive these treatments. The present study aimed to identify the novel regulatory genes in metastatic LUAD. Because the pleural cavity is a frequent metastasis site of LUAD, the adjacent non-tumor tissue, primary tumor tissue, and metastatic lung tumor tissue in the pleura of a single patient with LUAD were collected. The gene expression profiles of the collected samples were further analyzed via RNA sequencing and bioinformatic analysis. A high expression level of ubiquitin conjugating enzyme E2 H (UBE2H), a hypoxia-mediated gene, was identified in the metastatic malignant pleural tumor. After accessing the survival data in patients with lung adenocarcinoma through online databases, a high UBE2H expression was associated with poor survival for LUAD. UBE2H knockdown in two lung adenocarcinoma cell lines suppressed the cell migration capacity and reversed the epithelial–mesenchymal transition (EMT) signaling pathway. A high expression of UBE2H-targeting microRNAs, including miR-101, miR-30a, miR-30b, miR-328, and miR-497, were associated with a favorable prognosis. Moreover, the UBE2H expression revealed a significant correlation with the copy number variation. Taken together, the presence of UBE2H regulated the EMT program and metastasis in LUAD.https://www.mdpi.com/2079-7737/10/5/378lung adenocarcinomametastasishypoxiaubiquitin conjugating enzyme E2 H (UBE2H)RNA sequencingmicroRNA
spellingShingle Meng-Chi Yen
Kuan-Li Wu
Yu-Wei Liu
Yung-Yun Chang
Chao-Yuan Chang
Jen-Yu Hung
Ying-Ming Tsai
Ya-Ling Hsu
Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung Adenocarcinoma
Biology
lung adenocarcinoma
metastasis
hypoxia
ubiquitin conjugating enzyme E2 H (UBE2H)
RNA sequencing
microRNA
title Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung Adenocarcinoma
title_full Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung Adenocarcinoma
title_fullStr Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung Adenocarcinoma
title_full_unstemmed Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung Adenocarcinoma
title_short Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung Adenocarcinoma
title_sort ubiquitin conjugating enzyme e2 h ube2h is linked to poor outcomes and metastasis in lung adenocarcinoma
topic lung adenocarcinoma
metastasis
hypoxia
ubiquitin conjugating enzyme E2 H (UBE2H)
RNA sequencing
microRNA
url https://www.mdpi.com/2079-7737/10/5/378
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