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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2021-11-01
|
Series: | BMC Genomics |
Subjects: | |
Online Access: | https://doi.org/10.1186/s12864-021-08137-5 |
_version_ | 1818652169562226688 |
---|---|
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. |
first_indexed | 2024-12-17T02:17:44Z |
format | Article |
id | doaj.art-e2ad0849a2ad476fb109ff4b4278cb8f |
institution | Directory Open Access Journal |
issn | 1471-2164 |
language | English |
last_indexed | 2024-12-17T02:17:44Z |
publishDate | 2021-11-01 |
publisher | BMC |
record_format | Article |
series | BMC Genomics |
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 |
work_keys_str_mv | AT hongjinwu identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma AT weiweitian identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma AT xiangtai identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma AT xuanpengli identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma AT ziweili identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma AT jingshui identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma AT juehuayu identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma AT zhihuawang identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma AT xiaosongzhu identificationandfunctionalanalysisofnoveloncogeneddx60linpancreaticductaladenocarcinoma |