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

Publisher: BioMed Central Country of Publication: England NLM ID: 101147698 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-4598 (Electronic) Linking ISSN: 14764598 NLM ISO Abbreviation: Mol Cancer Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2002-

RNA, Circular*; Genes, myc/*genetics ; Hyaluronan Receptors/*genetics ; MicroRNAs/*genetics ; Proto-Oncogene Proteins p21(ras)/*genetics ; RNA-Binding Proteins/*genetics ; Triple Negative Breast Neoplasms/*genetics; Animals ; Apoptosis/genetics ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hyaluronan Receptors/chemistry ; Mice ; Oncogenes ; Prognosis ; RNA Interference ; Structure-Activity Relationship

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.
(© 2021. The Author(s).)

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82125024 China National Funds for Distinguished Young Scientists

Keywords: IGF2BP2; KRAS; MYC; TNBC; circCD44; circRNAs

0 (Biomarkers, Tumor)
0 (CD44 protein, human)
0 (Hyaluronan Receptors)
0 (IGF2BP2 protein, human)
0 (KRAS protein, human)
0 (MIRN502 microRNA, human)
0 (MicroRNAs)
0 (RNA, Circular)
0 (RNA-Binding Proteins)
EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))

Date Created: 20211026 Date Completed: 20220224 Latest Revision: 20220224

20221213

PMC8543802

10.1186/s12943-021-01444-1

34696797