Communications Biology ( IF 5.2 ) Pub Date : 2024-05-16 , DOI: 10.1038/s42003-024-06095-8 Xiao-Min Ran 1 , Juan Yang 1 , Zi-Yi Wang 1 , Ling-Zhi Xiao 1 , Yu-Ping Deng 1 , Ke-Qiang Zhang 1
Tumor-associated macrophages of the M2 phenotype promote cancer initiation and progression. Importantly, M2 macrophage-derived exosomes play key roles in the malignancy of cancer cells. Here, we report that circTMCO3 is upregulated in ovarian cancer patients, and its high expression indicates poor survival. M2-derived exosomes promote proliferation, migration, and invasion in ovarian cancer, but these effects are abolished by knockdown of circTMCO3. Furthermore, circTMCO3 functions as a competing endogenous RNA for miR-515-5p to reduce its abundance, thus upregulating ITGA8 in ovarian cancer. miR-515-5p inhibits ovarian cancer malignancy via directly downregulating ITGA8. The decreased oncogenic activity of circTMCO3-silencing exosomes is reversed by miR-515-5p knockdown or ITGA8 overexpression. Exosomal circTMCO3 promotes ovarian cancer progression in nude mice. Thus, M2 macrophage-derived exosomes promote malignancy by delivering circTMCO3 and targeting the miR-515-5p/ITGA8 axis in ovarian cancer. Our findings not only provide mechanistic insights into ovarian cancer progression, but also suggest potential therapeutic targets.
中文翻译:
M2巨噬细胞衍生的外泌体circTMCO3通过miR-515-5p和ITGA8发挥作用,增强卵巢癌的恶性程度
M2 表型的肿瘤相关巨噬细胞促进癌症的发生和进展。重要的是,M2巨噬细胞衍生的外泌体在癌细胞的恶性过程中发挥着关键作用。在这里,我们报告了circTMCO3在卵巢癌患者中表达上调,其高表达表明生存率较差。 M2 衍生的外泌体促进卵巢癌的增殖、迁移和侵袭,但这些作用可以通过敲除circTMCO3来消除。此外, circTMCO3作为miR-515-5p的竞争性内源 RNA,降低其丰度,从而上调卵巢癌中的 ITGA8。 miR-515-5p通过直接下调 ITGA8 抑制卵巢癌恶性肿瘤。 circTMCO3沉默外泌体的致癌活性降低可通过miR-515-5p敲低或 ITGA8 过表达来逆转。外泌体circTMCO3促进裸鼠卵巢癌进展。因此,M2巨噬细胞衍生的外泌体通过在卵巢癌中递送circTMCO3并靶向miR-515-5p / ITGA8轴来促进恶性肿瘤。我们的研究结果不仅提供了卵巢癌进展的机制见解,而且还提出了潜在的治疗靶点。