Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Aging (Albany NY). 2021 Mar 3;13(6):8115-8126. doi: 10.18632/aging.202608.
To explore the effect of circRHOT1 on breast cancer progression and the underlying mechanism. Significantly, our data revealed that the depletion of circRHOT1 was able to repress the proliferation and induce the apoptosis of breast cancer cells. CircRHOT1 knockdown could remarkably inhibit the invasion and migration in the breast cancer cells. Meanwhile, the depletion of circRHOT1 enhanced the erastin-induced inhibition effect on cell growth of breast cancer cells. The circRHOT1 knockdown notably increased the levels of reactive oxygen species (ROS), iron, and Fe in breast cancer cells. Mechanically, circRHOT1 was able to sponge microRNA-106a-5p (miR-106a-5p) and inhibited ferroptosis by down-regulating miR-106a-5p in breast cancer cells. Besides, miR-106a-5p induced ferroptosis by targeting signal transducer and activator of transcription 3 (STAT3) in the system. Moreover, the overexpression of STAT3 and miR-106a-5p inhibitor could reverse circRHOT1 knockdown-mediated breast cancer progression. Functionally, circRHOT1 promoted the tumor growth of breast cancer . In conclusion, we discovered that circRHOT1 contributed to malignant progression and attenuated ferroptosis in breast cancer by the miR-106a-5p/STAT3 axis. Our finding provides new insights into the mechanism by which circRHOT1 promotes the development of breast cancer. CircRHOT1 and miR-106a-5p may serve as potential targets for breast cancer therapy.
为了探究环状 RNA（circRNA）RHOT1 对乳腺癌进展的影响及其潜在机制。有研究数据表明，circRHOT1 的耗竭能够抑制乳腺癌细胞的增殖并诱导其凋亡。circRHOT1 敲低能够显著抑制乳腺癌细胞的侵袭和迁移。同时，circRHOT1 的耗竭增强了依拉司琼对乳腺癌细胞生长的抑制作用。circRHOT1 敲低显著增加了乳腺癌细胞内的活性氧（ROS）、铁和 Fe 水平。机制上，circRHOT1 能够通过海绵吸附 microRNA-106a-5p（miR-106a-5p）并下调乳腺癌细胞中的 miR-106a-5p 来抑制铁死亡。此外，miR-106a-5p 通过在该系统中靶向信号转导和转录激活因子 3（STAT3）诱导铁死亡。此外，STAT3 的过表达和 miR-106a-5p 抑制剂的转染能够逆转 circRHOT1 敲低介导的乳腺癌进展。功能上，circRHOT1 促进了乳腺癌的肿瘤生长。总之，我们发现 circRHOT1 通过 miR-106a-5p/STAT3 轴促进乳腺癌的恶性进展并减弱铁死亡。我们的研究结果为 circRHOT1 促进乳腺癌发展的机制提供了新的见解。circRHOT1 和 miR-106a-5p 可能成为乳腺癌治疗的潜在靶点。
