Zhang Yue, Tan Duxun, Xie Yi, Wu Linyu, Wu Song, Tang Yuhui, Luo Yongzhou, Xiao Xiangsheng, Li Xing
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
Kangyuan Hospital, Guangzhou, Guangdong, China.
J Oncol. 2022 Aug 26;2022:1028851. doi: 10.1155/2022/1028851. eCollection 2022.
Breast cancer is the most common type of cancer worldwide. There are great challenges in the prevention and treatment of breast cancer. In this study, we explored the molecular and biological mechanisms of circular RNA circEPSTI1 (has_circ_0000479) in the regulation of HER2-positive breast cancer cells. The expression of CircEPSTI1, microRNA miR-145, and ERBB3 in HER2-positive breast cancer cells was evaluated by qRT-PCR and western blot assays. Cell proliferation was assessed by CCK-8. Wound-healing and transwell migration assays were performed to evaluate cell migration. A transwell invasion assay was performed to detect cell invasion. The interaction of miR-145, circEPSTI1, and ERBB3 was confirmed bydual-luciferase reporter and RIP assays. CircEPSTI1 was upregulated in the HER2-positive breast cancer tissues and cells. Knockdown of circEPSTI1 inhibited SKBR3 and BT474 cell proliferation, migration, and invasion. Mechanistically, circEPSTI1 directly targeted miR-145, and miR-145 was a downstream mediator of circEPSTI1 in modulating the proliferation, migration, and invasion of SKBR3 and BT474 cells. ERBB3 was identified as a direct and functional target of miR-145 in HER2-positive breast cancer cells. Our findings demonstrate that circEPSTI1, an overexpressed circRNA in HER2-positive breast cancer, promotes the proliferation, migration, and invasion of SKBR3 and BT474 cells through the miR-145/ERBB3 axis.
乳腺癌是全球最常见的癌症类型。乳腺癌的预防和治疗面临巨大挑战。在本研究中，我们探讨了环状RNA circEPSTI1（has_circ_0000479）在调控HER2阳性乳腺癌细胞中的分子和生物学机制。通过qRT-PCR和蛋白质免疫印迹分析评估HER2阳性乳腺癌细胞中CircEPSTI1、微小RNA miR-145和ERBB3的表达。通过CCK-8评估细胞增殖。进行伤口愈合和Transwell迁移试验以评估细胞迁移。进行Transwell侵袭试验以检测细胞侵袭。通过双荧光素酶报告基因和RIP试验证实了miR-145、circEPSTI1和ERBB3之间的相互作用。CircEPSTI1在HER2阳性乳腺癌组织和细胞中上调。敲低circEPSTI1可抑制SKBR3和BT474细胞的增殖、迁移和侵袭。机制上，circEPSTI1直接靶向miR-145，并且miR-145是circEPSTI1调节SKBR3和BT474细胞增殖、迁移和侵袭的下游介质。在HER2阳性乳腺癌细胞中，ERBB3被鉴定为miR-145的直接和功能性靶标。我们的研究结果表明，circEPSTI1是HER2阳性乳腺癌中过表达的环状RNA，它通过miR-145/ERBB3轴促进SKBR3和BT474细胞的增殖、迁移和侵袭。
