Globally, breast cancer affects women more than any other type of cancer and is the leading cause of cancer-related death in women. Although aggressive surgery combined with radiotherapy, chemotherapy and hormonal therapy has achieved some efficacy, the therapeutic effect for some breast cancer patients is still limited. The advent of targeted therapies has changed the concept of cancer therapy, and both early and advanced breast cancer can be targeted by specific proteins or genes to improve clinical outcome. Therefore, there is an urgent need to discover more new targets to optimize current therapies and address the problem of acquired resistance.
Recently, researchers from Gannan Medical University are working at J Exp Clin Cancer Res. Published "Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF- κ B-IL-6 axis of tumor-associated macrophages", The study illuminates a novel mechanism, Namely, tumor xenosomal cSERPINE2 mediates a positive feedback loop between tumor cells and TAM, To promote the progression of the cancer, This could be a promising nanotherapeutic strategy for the treatment of breast cancer.
Circular RNA (circRNAs) has an important regulatory function in cancer, but its role in the tumor microenvironment (TME) is still unknown. The investigators explored the role of si-cirRNA loaded in nanoparticles as an anti-tumor therapeutic agent in vivo and performed bioinformatics analysis, qRT-PCR, EdU analysis, Transwell analysis, co-culture system and multiple orthotopic xenograft models to study circRNA expression and function. Furthermore, PLGA-based nanoparticles were used to evaluate the potential of nanotherapeutic strategies in antitumor responses.
The investigators identified the oncogene SERPINE2-derived circRNA, named cSERPINE, which is significantly elevated in cancer and is strongly associated with adverse clinical outcomes. Functionally, the external tumor body cSERPINE2 is transported to tumor-associated macrophages (TAM) and enhances the secretion of interleukin-6 (IL-6), leading to increased proliferation and invasion of breast cancer cells. Moreover, IL-6 in turn increased the EIF4A3 and CCL 2 levels within the tumor cells with a positive feedback mechanism, further enhancing the tumor cSERPINE2 biogenesis and promoting the recruitment of TAMs. More importantly, the researchers have developed a PLGA-based nanoparticle loaded with si-cSERPINE2, which can effectively slow down the progression of breast cancer in vivo.
In conclusion, this study revealed a novel mechanism by which the oncogene SERPINE2-derived hsa _ circ _ 0001103 (cSERPINE) plays a communication signaling role in the tumor immune microenvironment to promote breast cancer progression.
