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Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Approximately 80% of patients initially diagnosed with locally advanced or metastatic disease survive only 4–11 months after diagnosis. Tremendous efforts have been made toward understanding the biology of PDAC. RESULTS: In this...

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Autores principales: Wu, Hongjin, Tian, Weiwei, Tai, Xiang, Li, Xuanpeng, Li, Ziwei, Shui, Jing, Yu, Juehua, Wang, Zhihua, Zhu, Xiaosong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600871/
https://www.ncbi.nlm.nih.gov/pubmed/34789165
http://dx.doi.org/10.1186/s12864-021-08137-5
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author Wu, Hongjin
Tian, Weiwei
Tai, Xiang
Li, Xuanpeng
Li, Ziwei
Shui, Jing
Yu, Juehua
Wang, Zhihua
Zhu, Xiaosong
author_facet Wu, Hongjin
Tian, Weiwei
Tai, Xiang
Li, Xuanpeng
Li, Ziwei
Shui, Jing
Yu, Juehua
Wang, Zhihua
Zhu, Xiaosong
author_sort Wu, Hongjin
collection PubMed
description BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Approximately 80% of patients initially diagnosed with locally advanced or metastatic disease survive only 4–11 months after diagnosis. Tremendous efforts have been made toward understanding the biology of PDAC. RESULTS: In this study, we first utilized next-generation sequencing technique and existing microarray datasets to identify significant differentially expressed genes between PDAC and non-tumor adjacent tissue. By comparing top significant survival genes in PDAC Gene Expression Profiling Interactive Analysis database and PDAC transcriptome data from patients, our integrated analysis discovered five potential central genes (i.e., MYEOV, KCNN4, FAM83A, S100A16, and DDX60L). Subsequently, we analyzed the cellular functions of the potential novel oncogenes MYEOV and DDX60L, which are highly expressed in PDAC cells. Notably, the knockdown of MYEOV and DDX60L significantly inhibited the metastasis of cancer cells and induced apoptosis. Further RNA sequencing analyses showed that massive signaling pathways, particularly the TNF signaling pathway and nuclear factor-kappa B (NF-κB) signaling pathway, were affected in siRNA-treated cancer cells. The siDDX60L and siMYEOV significantly inhibited the expression of chemokine CXCL2, which may potentially affect the tumor microenvironment in PDAC tissues. CONCLUSIONS: The present findings identified the novel oncogene DDX60L, which was highly expressed in PDAC. Transcriptome profiling through siRNA knockdown of DDX60L uncovered its functional roles in the PDAC in humans. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-08137-5.
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spelling pubmed-86008712021-11-19 Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma Wu, Hongjin Tian, Weiwei Tai, Xiang Li, Xuanpeng Li, Ziwei Shui, Jing Yu, Juehua Wang, Zhihua Zhu, Xiaosong BMC Genomics Research BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Approximately 80% of patients initially diagnosed with locally advanced or metastatic disease survive only 4–11 months after diagnosis. Tremendous efforts have been made toward understanding the biology of PDAC. RESULTS: In this study, we first utilized next-generation sequencing technique and existing microarray datasets to identify significant differentially expressed genes between PDAC and non-tumor adjacent tissue. By comparing top significant survival genes in PDAC Gene Expression Profiling Interactive Analysis database and PDAC transcriptome data from patients, our integrated analysis discovered five potential central genes (i.e., MYEOV, KCNN4, FAM83A, S100A16, and DDX60L). Subsequently, we analyzed the cellular functions of the potential novel oncogenes MYEOV and DDX60L, which are highly expressed in PDAC cells. Notably, the knockdown of MYEOV and DDX60L significantly inhibited the metastasis of cancer cells and induced apoptosis. Further RNA sequencing analyses showed that massive signaling pathways, particularly the TNF signaling pathway and nuclear factor-kappa B (NF-κB) signaling pathway, were affected in siRNA-treated cancer cells. The siDDX60L and siMYEOV significantly inhibited the expression of chemokine CXCL2, which may potentially affect the tumor microenvironment in PDAC tissues. CONCLUSIONS: The present findings identified the novel oncogene DDX60L, which was highly expressed in PDAC. Transcriptome profiling through siRNA knockdown of DDX60L uncovered its functional roles in the PDAC in humans. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-08137-5. BioMed Central 2021-11-18 /pmc/articles/PMC8600871/ /pubmed/34789165 http://dx.doi.org/10.1186/s12864-021-08137-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wu, Hongjin
Tian, Weiwei
Tai, Xiang
Li, Xuanpeng
Li, Ziwei
Shui, Jing
Yu, Juehua
Wang, Zhihua
Zhu, Xiaosong
Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma
title Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma
title_full Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma
title_fullStr Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma
title_full_unstemmed Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma
title_short Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma
title_sort identification and functional analysis of novel oncogene ddx60l in pancreatic ductal adenocarcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600871/
https://www.ncbi.nlm.nih.gov/pubmed/34789165
http://dx.doi.org/10.1186/s12864-021-08137-5
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