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

Abstract 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...

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Autores principales: Hongjin Wu, Weiwei Tian, Xiang Tai, Xuanpeng Li, Ziwei Li, Jing Shui, Juehua Yu, Zhihua Wang, Xiaosong Zhu
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Publicado: BMC 2021
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spelling oai:doaj.org-article:e2ad0849a2ad476fb109ff4b4278cb8f2021-11-21T12:26:29ZIdentification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma10.1186/s12864-021-08137-51471-2164https://doaj.org/article/e2ad0849a2ad476fb109ff4b4278cb8f2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12864-021-08137-5https://doaj.org/toc/1471-2164Abstract 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.Hongjin WuWeiwei TianXiang TaiXuanpeng LiZiwei LiJing ShuiJuehua YuZhihua WangXiaosong ZhuBMCarticlePancreatic ductal adenocarcinoma (PDAC)OncogeneDDX60LMYEOVCXCL2BiotechnologyTP248.13-248.65GeneticsQH426-470ENBMC Genomics, Vol 22, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Pancreatic ductal adenocarcinoma (PDAC)
Oncogene
DDX60L
MYEOV
CXCL2
Biotechnology
TP248.13-248.65
Genetics
QH426-470
spellingShingle Pancreatic ductal adenocarcinoma (PDAC)
Oncogene
DDX60L
MYEOV
CXCL2
Biotechnology
TP248.13-248.65
Genetics
QH426-470
Hongjin Wu
Weiwei Tian
Xiang Tai
Xuanpeng Li
Ziwei Li
Jing Shui
Juehua Yu
Zhihua Wang
Xiaosong Zhu
Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma
description Abstract 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.
format article
author Hongjin Wu
Weiwei Tian
Xiang Tai
Xuanpeng Li
Ziwei Li
Jing Shui
Juehua Yu
Zhihua Wang
Xiaosong Zhu
author_facet Hongjin Wu
Weiwei Tian
Xiang Tai
Xuanpeng Li
Ziwei Li
Jing Shui
Juehua Yu
Zhihua Wang
Xiaosong Zhu
author_sort Hongjin Wu
title 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_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_sort identification and functional analysis of novel oncogene ddx60l in pancreatic ductal adenocarcinoma
publisher BMC
publishDate 2021
url https://doaj.org/article/e2ad0849a2ad476fb109ff4b4278cb8f
work_keys_str_mv AT hongjinwu identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma
AT weiweitian identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma
AT xiangtai identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma
AT xuanpengli identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma
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AT xiaosongzhu identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma
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