Yanmei Zou1, Shuo Yao1, Xiuqiong Chen1, Dian Liu1, Jianhua Wang1, Xun Yuan1, Jie Rao1, Huihua Xiong1, Shiying Yu1, Xianglin Yuan1, Feng Zhu2, Guohong Hu3, Yihua Wang4, Hua Xiong5. 1. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. 3. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological, Shanghai, 200031, China. 4. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO171BJ, UK. 5. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: xshzxz@163.com.
Abstract
OBJECT: This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells. METHODS: Microarray analysis was used to screen out lncRNAs differentially expressed in radio-resistant CRC cell lines. Expression levels of OIP5-AS1, miR-369-3p and DYRK1A in CRC cell lines were measured by qRT-PCR. Protein expression of DYRK1A was determined by western blot. The target relationships among OIP5-AS1, miR-369-3p and DYRK1A were validated by dual luciferase reporter assay. Impacts of OIP5-AS1 or DYRK1A on CRC cellular activity and apoptosis were investigated by MTT assay, clonogenic survival assay and flow cytometry to analyze OIP5-AS1 or DYRK1A's effect on radioresistance of CRC cells. RESULTS: LncRNA OIP5-AS1 and DYRK1A were down-regulated in radio-resistant CRC cell lines. OIP5-AS1 suppressed the expression of miR-369-3p, thus up-regulating DYRK1A, the downstream gene of miR-369-3p. OIP5-AS1 and DYRK1A impaired cell clonogenic survival and promoted cell apoptosis after irradiation, improving radiosensitivity of CRC cells. CONCLUSION: LncRNA OIP5-AS1 suppressed cell viability, promoted radio-induced apoptosis, and enhanced the radiosensitivity of CRC cells by regulating DYRK1A expression through miR-369-3p.
OBJECT: This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells. METHODS: Microarray analysis was used to screen out lncRNAs differentially expressed in radio-resistant CRC cell lines. Expression levels of OIP5-AS1, miR-369-3p and DYRK1A in CRC cell lines were measured by qRT-PCR. Protein expression of DYRK1A was determined by western blot. The target relationships among OIP5-AS1, miR-369-3p and DYRK1A were validated by dual luciferase reporter assay. Impacts of OIP5-AS1 or DYRK1A on CRC cellular activity and apoptosis were investigated by MTT assay, clonogenic survival assay and flow cytometry to analyze OIP5-AS1 or DYRK1A's effect on radioresistance of CRC cells. RESULTS: LncRNA OIP5-AS1 and DYRK1A were down-regulated in radio-resistant CRC cell lines. OIP5-AS1 suppressed the expression of miR-369-3p, thus up-regulating DYRK1A, the downstream gene of miR-369-3p. OIP5-AS1 and DYRK1A impaired cell clonogenic survival and promoted cell apoptosis after irradiation, improving radiosensitivity of CRC cells. CONCLUSION: LncRNA OIP5-AS1 suppressed cell viability, promoted radio-induced apoptosis, and enhanced the radiosensitivity of CRC cells by regulating DYRK1A expression through miR-369-3p.