Frontiers in Oncology (Aug 2020)
CircHIPK3 Promotes Metastasis of Gastric Cancer via miR-653-5p/miR-338-3p-NRP1 Axis Under a Long-Term Hypoxic Microenvironment
- Yue Jin,
- Yue Jin,
- Yue Jin,
- Yue Jin,
- Xiaofang Che,
- Xiaofang Che,
- Xiaofang Che,
- Xiaofang Che,
- Xiujuan Qu,
- Xiujuan Qu,
- Xiujuan Qu,
- Xiujuan Qu,
- Xin Li,
- Wenqing Lu,
- Wenqing Lu,
- Wenqing Lu,
- Wenqing Lu,
- Jie Wu,
- Jie Wu,
- Jie Wu,
- Jie Wu,
- Yizhe Wang,
- Yizhe Wang,
- Yizhe Wang,
- Yizhe Wang,
- Kezuo Hou,
- Kezuo Hou,
- Kezuo Hou,
- Kezuo Hou,
- Ce Li,
- Ce Li,
- Ce Li,
- Ce Li,
- Xiaojie Zhang,
- Xiaojie Zhang,
- Xiaojie Zhang,
- Xiaojie Zhang,
- Jianping Zhou,
- Yunpeng Liu,
- Yunpeng Liu,
- Yunpeng Liu,
- Yunpeng Liu
Affiliations
- Yue Jin
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yue Jin
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yue Jin
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Yue Jin
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Xiaofang Che
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Xiaofang Che
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Xiaofang Che
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Xiaofang Che
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Xiujuan Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Xiujuan Qu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Xiujuan Qu
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Xiujuan Qu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Xin Li
- Department of Gastrointestinal Surgery, The First Hospital of China Medical University, Shenyang, China
- Wenqing Lu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Wenqing Lu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Wenqing Lu
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Wenqing Lu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Jie Wu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Jie Wu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Jie Wu
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Jie Wu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Yizhe Wang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yizhe Wang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yizhe Wang
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Yizhe Wang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Kezuo Hou
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Kezuo Hou
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Kezuo Hou
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Kezuo Hou
- 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
- Xiaojie Zhang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Xiaojie Zhang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Xiaojie Zhang
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Xiaojie Zhang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- Jianping Zhou
- Department of Gastrointestinal Surgery, The First Hospital of China Medical University, Shenyang, China
- Yunpeng Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yunpeng Liu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yunpeng Liu
- Liaoning Province Clinical Research Center for Cancer, Shenyang, China
- Yunpeng Liu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, China
- DOI
- https://doi.org/10.3389/fonc.2020.01612
- Journal volume & issue
-
Vol. 10
Abstract
As a vital feature of the microenvironment, hypoxia, especially long-term hypoxia, is known to promote metastasis and lead to poor prognosis in solid tumors. Circular RNAs (circRNAs) participate in important processes of cell proliferation and metastasis in cancers. However, the contribution of circRNAs to metastasis under long-term hypoxia is obscure. In this study, we aim to explore specific functions of circHIPK3 in long-term hypoxia-promoting metastasis of gastric cancer (GC). The hypoxic resistant gastric cancer (HRGC) cell lines we established previously, which were tolerant to 2% O2 conditions, were used as the long-term hypoxia model. We found that circHIPK3 was upregulated by HIF-2α in HRGC cells, and circHIPK3 facilitated the migration and invasion ability of HRGC cells. Further investigation proved that circHIPK3 promoted metastasis of HRGC cells directly by interacting with miR-653-5p and miR-338-3p to relieve the suppression of neuropilin 1 (NRP1), resulting in the activation of downstream ERK and AKT pathways. Our study identified oncogene functions of circHIPK3 under a long-term hypoxic microenvironment and the possibility of using circHIPK3 as a potential biomarker of long-term hypoxia in GC. In conclusion, circHIPK3 could promote GC metastasis via the miR-653-5p/miR-338-3p-NRP1 axis under a long-term hypoxic microenvironment.
Keywords
