Li Chunxiang, Liu Hengchang, Wei Ran, Liu Zheng, Chen Haipeng, Guan Xu, Zhao Zhixun, Wang Xishan, Jiang Zheng
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.
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.
Onco Targets Ther. 2021 Apr 28;14:2867-2878. doi: 10.2147/OTT.S256989. eCollection 2021.
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.
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.
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.
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.
背景/目的：长链非编码核糖核酸（lncRNAs）参与癌症进展并影响放射治疗反应。本研究旨在探讨lncRNA EGOT在直肠癌放射敏感性中的作用机制。
采用qRT-PCR检测直肠癌组织及细胞中EGOT、miR-211-5p和ErbB4的mRNA表达。采用蛋白质免疫印迹法检测ErbB4的蛋白表达。采用双荧光素酶报告基因检测法和核糖核酸免疫沉淀法（RIP）证实EGOT与miR-211-5p或miR-211-5p与ErbB4之间的相互作用。分别采用转染技术下调和上调直肠癌细胞中EGOT和miR-211-5p的表达。采用MTT法、集落形成实验和流式细胞术检测EGOT和miR-211-5p对直肠癌细胞增殖、侵袭、迁移和凋亡的影响。
EGOT在直肠癌组织和细胞中表达上调，且EGOT的表达与病理晚期相关。敲低EGOT可抑制直肠癌细胞的增殖和集落形成，并诱导直肠癌细胞凋亡。此外，敲低EGOT可显著增强放疗对体内外直肠癌的作用。此外，发现EGOT作为miR-211-5p的海绵，而ErbB4是miR-211-5p的下游靶点。EGOT通过调控miR-211-5p增强ErbB4的表达。miR-211-5p抑制剂可恢复敲低EGOT对直肠癌放射敏感性的影响。
下调EGOT可通过调控miR-211-5p/ErbB4轴抑制直肠癌细胞生长，提高直肠癌细胞的放射敏感性。EGOT可能是直肠癌的一个新的治疗靶点。
