RESUMO
The expression of hypoxia-inducible factors (HIFs), particularly HIF-1, plays a major role in the adaptation of solid tumors to hypoxic conditions. The activation of the HIF pathway results in an expression of genes involved in the promotion of cell growth, proliferation, vascularization, metastasis, and therapeutic resistance. Circular RNA (CircRNA) is considered as a major regulator of gene expression. CircRNAs could regulate the HIF-1 pathway in cancer cells. In addition, they might be regulated by the HIF-1 pathway to promote cancer progression. Therefore, the crosstalk between hypoxia and circRNA might be involved in the pathogenesis of cancers, including breast cancer. In this review, we discussed the function of HIF-related circRNAs in the progression, angiogenesis, metabolic reprogramming, and stemness maintenance of breast cancer. In addition, the correlation between HIF-related circRNAs and clinical features of breast cancer is reviewed.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , RNA Circular/genética , Hipóxia/metabolismo , Neovascularização Patológica/genética , Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Regulação Neoplásica da Expressão Gênica/genéticaRESUMO
Cancer stem cells (CSCs) as a small subpopulation in tumor bulk are believed to initiate tumor formation and are responsible for the resistance to cancer therapy. The proliferation and differentiation of CSCs result in heterogeneity in a tumor which increases the chance of tumor survival and invasion. Many signaling pathways are abnormally activated or repressed in CSCs. Understanding these pathways and the metabolisms in CSCs may help targeted therapy in drug-resistant tumors. The PI3K/Akt/mTOR pathway is one of the major signaling pathways in CSCs involved in the maintenance of stemness, proliferation, differentiation, epithelial to mesenchymal transition (EMT), migration, and autophagy. Thus, suppressing the PI3K/Akt/mTOR pathway with inhibitors might be a promising strategy for targeted cancer therapy. Although the pathway is well-recognized and reviewed in tumor bulks, the functions in CSCs have not been well focused. Here, we reviewed the PI3K/Akt/mTOR signaling pathway and its functions in CSCs and addressed the potential therapeutic applications in drug-resistant tumors.
