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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Main Authors: Hongjin Wu, Weiwei Tian, Xiang Tai, Xuanpeng Li, Ziwei Li, Jing Shui, Juehua Yu, Zhihua Wang, Xiaosong Zhu
Format: Article
Language:English
Published: BMC 2021-11-01
Series:BMC Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12864-021-08137-5
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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
collection DOAJ
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.
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spelling doaj.art-e2ad0849a2ad476fb109ff4b4278cb8f2022-12-21T22:07:21ZengBMCBMC Genomics1471-21642021-11-0122111410.1186/s12864-021-08137-5Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinomaHongjin Wu0Weiwei Tian1Xiang Tai2Xuanpeng Li3Ziwei Li4Jing Shui5Juehua Yu6Zhihua Wang7Xiaosong Zhu8The NHC Key Laboratory of Drug Addiction Medicine, The First Affiliated Hospital of Kunming Medical UniversityYunnan Province Clinical Center for Bone and joint Diseases, The First Affiliated Hospital of Kunming Medical UniversityYunnan Province Clinical Center for Bone and joint Diseases, The First Affiliated Hospital of Kunming Medical UniversityYunnan Province Clinical Center for Bone and joint Diseases, The First Affiliated Hospital of Kunming Medical UniversityThe NHC Key Laboratory of Drug Addiction Medicine, The First Affiliated Hospital of Kunming Medical UniversityShanghai International Travel Healthcare CenterThe NHC Key Laboratory of Drug Addiction Medicine, The First Affiliated Hospital of Kunming Medical UniversityYunnan Province Clinical Center for Bone and joint Diseases, The First Affiliated Hospital of Kunming Medical UniversityYunnan Province Clinical Center for Bone and joint Diseases, The First Affiliated Hospital of Kunming Medical UniversityAbstract 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.https://doi.org/10.1186/s12864-021-08137-5Pancreatic ductal adenocarcinoma (PDAC)OncogeneDDX60LMYEOVCXCL2
spellingShingle 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
BMC Genomics
Pancreatic ductal adenocarcinoma (PDAC)
Oncogene
DDX60L
MYEOV
CXCL2
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 Pancreatic ductal adenocarcinoma (PDAC)
Oncogene
DDX60L
MYEOV
CXCL2
url https://doi.org/10.1186/s12864-021-08137-5
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