环状 RNA CD44 通过调节 miR-502-5p/KRAS 和 IGF2BP2/Myc 轴在三阴性乳腺癌中发挥致癌作用。
CircCD44 plays oncogenic roles in triple-negative breast cancer by modulating the miR-502-5p/KRAS and IGF2BP2/Myc axes.
机构信息
Department of Thyroid and Breast Surgery, The First Affiliate Hospital, Sun Yat-sen University, No 58, Zhongshan 2 Road, Guangzhou, 510080, Guangdong Province, China.
Department of Neurosurgery, The First Affiliate Hospital, Sun Yat-sen University, No 58, Zhongshan 2 Road, Guangzhou, 510080, Guangdong Province, China.
出版信息
Mol Cancer. 2021 Oct 25;20(1):138. doi: 10.1186/s12943-021-01444-1.
BACKGROUND
Emerging studies have revealed the potent functions of circRNAs in breast cancer tumorigenesis. However, the biogenesis, biofunction and mechanism of circRNAs in triple-negative breast cancer (TNBC) are largely unknown.
METHODS
High-throughput RNA sequencing was applied to identify dysregulated circRNAs in TNBCs and paired normal tissues. RNA pulldown and luciferase assays were performed to investigate the interaction between circular CD44 (circCD44, also annotated as hsa_circ_0021735) and miR-502-5p. RNA pulldown and RIP assays were used to investigate the interaction between circCD44 and IGF2BP2. Cell viability, colony formation, migration/invasion assays and in vivo tumorigenesis were used to investigate circCD44 biological functions.
RESULTS
CircCD44 is an uncharacterized circRNA, which is highly expressed in TNBC, and its expression is negatively correlated with the prognosis of TNBC patients. CircCD44 promotes TNBC proliferation, migration, invasion and tumorigenesis at least partially by sponging miR-502-5p and interacting with IGF2BP2.
CONCLUSION
Our data suggested that overexpressed circCD44 promotes TNBC progression. CircCD44 is potentially a novel diagnostic and therapeutic marker for TNBC patients.
背景
新兴研究揭示了 circRNAs 在乳腺癌肿瘤发生中的强大功能。然而，circRNAs 在三阴性乳腺癌（TNBC）中的生物发生、生物功能和机制在很大程度上尚不清楚。
方法
采用高通量 RNA 测序鉴定 TNBC 组织和配对正常组织中失调的 circRNAs。进行 RNA 下拉和荧光素酶测定以研究环状 CD44（circCD44，也注释为 hsa_circ_0021735）与 miR-502-5p 之间的相互作用。采用 RNA 下拉和 RIP 测定研究 circCD44 与 IGF2BP2 之间的相互作用。通过细胞活力、集落形成、迁移/侵袭测定和体内肿瘤发生实验来研究 circCD44 的生物学功能。
结果
circCD44 是一种尚未被描述的 circRNA，在 TNBC 中高表达，其表达与 TNBC 患者的预后呈负相关。circCD44 通过海绵吸附 miR-502-5p 和与 IGF2BP2 相互作用至少部分促进 TNBC 的增殖、迁移、侵袭和肿瘤发生。
结论
我们的数据表明，circCD44 的过表达促进了 TNBC 的进展。circCD44 可能是 TNBC 患者的一种新型诊断和治疗标志物。
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