CircCD44 plays oncogenic roles in triple-negative breast cancer by modulating the miR-502-5p/KRAS and IGF2BP2/Myc axes

• Published in: Molecular cancer 2021-10, Vol.20 (1), p.138-138, Article 138
• Main Authors: Li, Jie, Gao, Xinya, Zhang, Zhanqiang, Lai, Yuanhui, Lin, Xunxun, Lin, Bo, Ma, Maoguang, Liang, Xiaoli, Li, Xixi, Lv, Weiming, Lin, Ying, Zhang, Nu
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Apoptosis; Apoptosis - genetics; Biomarkers; Biomarkers, Tumor - genetics; Breast cancer; CD44 antigen; Cell growth; Cell Line, Tumor; Cell migration; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell viability; circCD44; circRNAs; Cyclin-dependent kinases; Disease Progression; FDA approval; Female; Flow cytometry; Gene Expression Regulation, Neoplastic; Genes, myc - genetics; Humans; Hyaluronan Receptors - chemistry; Hyaluronan Receptors - genetics; IGF2BP2; K-Ras protein; Kinases; KRAS; Laboratory animals; Medical research; Medicine, Experimental; Mice; MicroRNAs; MicroRNAs - genetics; MYC; Myc protein; Oncogenes; Penicillin G; Pertuzumab; Plasmids; Prognosis; Proteins; Proto-Oncogene Proteins p21(ras) - genetics; Ribonucleic acid; RNA; RNA Interference; RNA sequencing; RNA, Circular; RNA-Binding Proteins - genetics; Structure-Activity Relationship; TNBC; Triple Negative Breast Neoplasms - genetics; Tumorigenesis
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-021-01444-1

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. 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. 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. Our data suggested that overexpressed circCD44 promotes TNBC progression. CircCD44 is potentially a novel diagnostic and therapeutic marker for TNBC patients.