Circular RNA RHOT1 promotes progression and inhibits ferroptosis via mir-106a-5p/STAT3 axis in breast cancer

Abstract

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 2+ 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 vivo . 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.

Circular RNA Circ_0067934 Attenuates Ferroptosis of Thyroid Cancer Cells by miR-545-3p/SLC7A11 Signaling

“…Moreover, apoptosis and ferroptosis are both crucial phenotypes during cancer development. As several previous reports ( 19 , 25 – 27 ), silencing the circ_0067934 not only induces cell ferroptosis but also causes cell apoptosis. The authors should distinguish which is the main cause of the observed cell death in future investigations, despite it is difficult and complicated.…”

circRNA hsa_circ_0005909 Predicts Poor Prognosis and Promotes the Growth, Metastasis, and Drug Resistance of Non-Small-Cell Lung Cancer via the miRNA-338-3p/SOX4 Pathway

“…For instance, circ_0110757 was reported to increase temozolomide resistance in neuroblastoma via sponging miRNA-1298-5p [ 25 ]. Circular RNA RHOT1 promoted metastasis and suppressed ferroptosis via the miR-106a-5p/STAT3 axis in breast cancer [ 26 ]. Previously, circ_0005909 was shown to sponge miRNA-338-3p and miR-936 in osteosarcoma, thus promoting the progression of osteosarcoma [ 13 , 22 ].…”

A Promising Future of Ferroptosis in Tumor Therapy

“… Wu et al (2020) concluded that the overexpression of glycogen synthase kinase-3β enhanced the therapeutic effect of erastin-triggered ferroptosis in breast tumors. Besides, Zhang et al (2021) found that circRHOT1-induced ferroptosis could be inhibited by the upregulation of STAT3 and miR-106a-5p in breast cancer. It is necessary to find more valuable targets and make rational use of targeted drugs to trigger ferroptosis, thereby enhancing the sensitivity of anti-tumor drugs in breast cancer.…”