LncRNA OIP5-AS1 regulates radioresistance by targeting DYRK1A through miR-369-3p in colorectal cancer cells

Yanmei Zou; Shuo Yao; Xiuqiong Chen; Dian Liu; Jianhua Wang; Xun Yuan; Jie Rao; Huihua Xiong; Shiying Yu; Xianglin Yuan; Feng Zhu; Guohong Hu; Yihua Wang; Hua Xiong

doi:10.1016/j.ejcb.2018.04.005

LncRNA OIP5-AS1 regulates radioresistance by targeting DYRK1A through miR-369-3p in colorectal cancer cells

Eur J Cell Biol. 2018 Jun;97(5):369-378. doi: 10.1016/j.ejcb.2018.04.005. Epub 2018 Apr 14.

Authors

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

Affiliations

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.

PMID: 29773344
DOI: 10.1016/j.ejcb.2018.04.005

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.

Keywords: Colorectal cancer; DYRK1A; OIP5-AS1; miR-369-3p.

MeSH terms

Apoptosis / genetics
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology
Colorectal Neoplasms / radiotherapy*
Down-Regulation
Dyrk Kinases
HEK293 Cells
Humans
MicroRNAs / genetics*
MicroRNAs / metabolism
Microarray Analysis / methods
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
Protein-Tyrosine Kinases / genetics*
Protein-Tyrosine Kinases / metabolism
RNA, Long Noncoding / genetics*
Radiation Tolerance / genetics

Substances

MicroRNAs
Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases
RNA, Long Noncoding
Dyrk Kinases
MIRN369 microRNA, human
long noncoding RNA OIP5, human