LncRNA EGOT/miR-211-5p Affected Radiosensitivity of Rectal Cancer by Competitively Regulating ErbB4

Chunxiang Li; Hengchang Liu; Ran Wei; Zheng Liu; Haipeng Chen; Xu Guan; Zhixun Zhao; Xishan Wang; Zheng Jiang

doi:10.2147/OTT.S256989

LncRNA EGOT/miR-211-5p Affected Radiosensitivity of Rectal Cancer by Competitively Regulating ErbB4

Onco Targets Ther. 2021 Apr 28:14:2867-2878. doi: 10.2147/OTT.S256989. eCollection 2021.

Authors

Chunxiang Li¹, Hengchang Liu², Ran Wei², Zheng Liu², Haipeng Chen², Xu Guan², Zhixun Zhao², Xishan Wang², Zheng Jiang²

Affiliations

¹ Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
² Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Abstract

Background/aims: Long non-coding ribonucleic acids (lncRNAs) are involved in the progression of cancers and affect the response to radiation therapy. This study was to investigate the mechanism of lncRNA EGOT in the radiosensitivity of rectal cancer.

Methods: The mRNA expression of EGOT, miR-211-5p and ErbB4 in rectal cancer tissues and cells was detected by qRT-PCR. The protein expression of ErbB4 was detected by Western blot. Dual-luciferase reporter assay and ribonucleic acid immunoprecipitation (RIP) were used to confirm the interaction between EGOT and miR-211-5p or miR-211-5p and ErbB4. Transfection technology was used to down-regulate and up-regulate the expression of EGOT and miR-211-5p in rectal cancer cells, respectively. MTT, colony formation and flow cytometry were used to detect the effect of EGOT and miR-211-5p on proliferation, invasion, migration and apoptosis of rectal cancer cells.

Results: The expression of EGOT was up-regulated in rectal cancer tissues and cells, and the expression of EGOT was related to the late stage of pathology. EGOT knockdown inhibited the proliferation and colony formation of rectal cancer cells and induced the apoptosis of rectal cancer cells. Moreover, EGOT knockdown was significantly enhanced the effects of radiotherapy on rectal cancer in vivo and in vitro. Furthermore, EGOT was found to serve as a sponge of miR-211-5p, and ErbB4 was a downstream target of miR-211-5p. EGOT enhanced the expression of ErbB4 by regulating miR-211-5p. MiR-211-5p inhibitor restored the effect of EGOT knockdown on the radiosensitivity of rectal cancer.

Conclusion: Down-regulation of EGOT could inhibit the growth of rectal cancer cells by regulating the miR-211-5p/ErbB4 axis and improve the radiosensitivity of rectal cancer cells. EGOT may be a new therapeutic target for rectal cancer.

Keywords: EGOT; ErbB4; miR-211-5p; radiosensitivity; rectal cancer.

Grants and funding

This work was supported by National Natural Science Foundation of China (81972196), National Key Research and Development Program of the Ministry of Science and Technology of China (2016YFC1303201, 2016YFC0905300, 2018YFC1315000), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32012), CAMS Innovation Fund for Medical Sciences (CIFMS) (2017-I2M-1-006, 2019-I2M-2-002), and Beijing Hope Run Special Fund from Cancer Foundation of China (LC2017A19).