Frontiers in Cell and Developmental Biology (Oct 2021)
RETRACTED: NR2F1-AS1/miR-190a/PHLDB2 Induces the Epithelial–Mesenchymal Transformation Process in Gastric Cancer by Promoting Phosphorylation of AKT3
- Jinqi Lv,
- Jinqi Lv,
- Jinqi Lv,
- Jinqi Lv,
- Simeng Zhang,
- Simeng Zhang,
- Simeng Zhang,
- Simeng Zhang,
- Yang Liu,
- Yang Liu,
- Yang Liu,
- Yang Liu,
- Ce Li,
- Ce Li,
- Ce Li,
- Ce Li,
- Tianshu Guo,
- Tianshu Guo,
- Tianshu Guo,
- Tianshu Guo,
- Shuairan Zhang,
- Shuairan Zhang,
- Shuairan Zhang,
- Shuairan Zhang,
- Zenan Li,
- Zenan Li,
- Zenan Li,
- Zenan Li,
- Zihan Jiao,
- Zihan Jiao,
- Zihan Jiao,
- Zihan Jiao,
- Haina Sun,
- Haina Sun,
- Haina Sun,
- Haina Sun,
- Ye Zhang,
- Ling Xu,
- Ling Xu,
- Ling Xu,
- Ling Xu
Affiliations
- Jinqi Lv
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Jinqi Lv
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Jinqi Lv
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Jinqi Lv
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Simeng Zhang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Simeng Zhang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Simeng Zhang
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Simeng Zhang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Yang Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yang Liu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yang Liu
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Yang Liu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Ce Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Ce Li
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Ce Li
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Ce Li
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Tianshu Guo
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Tianshu Guo
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Tianshu Guo
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Tianshu Guo
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Shuairan Zhang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Shuairan Zhang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Shuairan Zhang
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Shuairan Zhang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Zenan Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Zenan Li
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Zenan Li
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Zenan Li
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Zihan Jiao
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Zihan Jiao
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Zihan Jiao
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Zihan Jiao
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Haina Sun
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Haina Sun
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Haina Sun
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Haina Sun
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Ye Zhang
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China
- Ling Xu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Ling Xu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Ling Xu
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Ling Xu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- DOI
- https://doi.org/10.3389/fcell.2021.688949
- Journal volume & issue
-
Vol. 9
Abstract
The median survival time of patients with advanced gastric cancer (GC) who received radiotherapy and chemotherapy was <1 year. Epithelial–mesenchymal transformation (EMT) gives GC cells the ability to invade, which is an essential biological mechanism in the progression of GC. The long non-coding RNA (lncRNA)-based competitive endogenous RNA (ceRNA) system has been shown to play a key role in the GC-related EMT process. Although the AKT pathway is essential for EMT in GC, the relationship between AKT3 subtypes and EMT in GC is unclear. Here, we evaluated the underlying mechanism of ceRNA involving NR2F1-AS1/miR-190a/PHLDB2 in inducing EMT by promoting the expression and phosphorylation of AKT3. The results of bioinformatics analysis showed that the expression of NR2F1-AS1/miR-190a/PHLDB2 in GC was positively associated with the pathological features, staging, poor prognosis, and EMT process. We performed cell transfection, qRT-PCR, western blot, cell viability assay, TUNEL assay, Transwell assay, cell morphology observation, and double luciferase assay to confirm the regulation of NR2F1-AS1/miR-190a/PHLDB2 and its effect on EMT transformation. Finally, GSEA and GO/KEGG enrichment analysis identified that PI3K/AKT pathway was positively correlated to NR2F1-AS1/miR-190a/PHLDB2 expression. AKT3 knockout cells were co-transfected with PHLDB2-OE, and the findings revealed that AKT3 expression and phosphorylation were essential for the PHLDB2-mediated EMT process. Thus, our results showed that NR2F1-AS1/miR-190a/PHLDB2 promoted the phosphorylation of AKT3 to induce EMT in GC cells. This study provides a comprehensive understanding of the underlying mechanism involved in the EMT process as well as the identification of new EMT markers.
Keywords
