Abstract
Background
Triple Negative Breast Cancer (TNBC) is 1 of the most serious cancer. Circular RNA_0001777
(circ_0001777) expression was decreased in TNBC tissues. However, the molecular mechanism
of circ_0001777 remains unknown.
Methods
The expression of circ_0001777, microRNA-95-3p (miR-95-3p) and A-kinase anchor protein
12 (AKAP12) were detected by quantitative real-time fluorescence polymerase chain
reaction (qRT-PCR). A series of in vitro experiments were designed to explore the
function of circ_0001777 in TNBC cells and the regulatory mechanism between circ_0001777
and miR-95-3p and AKAP12 in TNBC cells. Western blot examined the relative protein
levels in TNBC cells. Bioinformatics prediction site predicted the relationship between
miR-95-3p and circ_0001777 or AKAP12 and was verified by Dual-luciferase reporter
assays. The xenotransplantation model was established to study the role of circ_0001777
in vivo.
Results
The expression of circ_0001777 and AKAP12 was decreased in TNBC tissues, while the
expression of miR-95-3p was increased. Circ_0001777 can sponge miR-95-3p, and AKAP12
is the target of miR-95-3p. In vitro complement experiments, overexpression of circ_0001777
significantly decreased the malignant behavior of TNBC, while co-transfection of miR-95-3p
partially up-regulated this change. In addition, AKAP12 knockdown increased the proliferation,
migration, and invasion of TNBC cells inhibited by overexpression of circ_0001777.
Mechanically, circ_0001777 regulates AKAP12 expression in TNBC cells by sponge miR-95-3p.
In addition, in vivo studies have shown that overexpression of circ_0001777 inhibits tumor growth.
Conclusion
Overexpression of circ_0001777 decreased proliferation, migration, and invasion of
TNBC cells by regulating the miR-95-3p/AKAP12 axis, suggesting that circ_0001777/miR-95-3p/AKAP12
axis may be a potential regulatory mechanism for the treatment of TNBC.
Keywords
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References
- Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2018; 68: 394-424
- Triple-negative breast cancer: disease entity or title of convenience?.Nat Rev Clin Oncol. 2010; 7: 683-692
- An overview of triple-negative breast cancer.Arch Gynecol Obstet. 2016; 293: 247-269
- Updates in the treatment of basal/triple-negative breast cancer.Curr Opin Obstet Gynecol. 2013; 25: 40-48
- Regulation of circRNA biogenesis.RNA Biol. 2015; 12: 381-388
- Circles reshaping the RNA world: from waste to treasure.Mol Cancer. 2017; 16: 58
- CircRNAs and cancer: biomarkers and master regulators.Semin Cancer Biol. 2019; 58: 90-99
- Circ_0000520 contributes to triple-negative breast cancer progression through mediating the miR-1296/ZFX axis.Thorac Cancer. 2021; 12: 2427-2438
- Circular RNA and miR-7 in cancer.Cancer Res. 2013; 73: 5609-5612
- Cell-type specific features of circular RNA expression.PLoS Genet. 2013; 9e1003777
- circFBXW7 Inhibits Malignant Progression by Sponging miR-197-3p and Encoding a 185-aa Protein in Triple-Negative Breast Cancer.Mol Ther Nucleic Acids. 2019; 18: 88-98
- CircUBE2D2 (hsa_circ_0005728) promotes cell proliferation, metastasis and chemoresistance in triple-negative breast cancer by regulating miR-512-3p/CDCA3 axis.Cancer Cell Int. 2020; 20: 454
- circUSP42 Is downregulated in triple-negative breast cancer and associated with poor prognosis.Technol Cancer Res Treat. 2020; 191533033820950827
- MicroRNAs in the etiology of colorectal cancer: pathways and clinical implications.Dis Model Mech. 2017; 10: 197-214
- Overexpression of miR-361-5p in triple-negative breast cancer (TNBC) inhibits migration and invasion by targeting RQCD1 and inhibiting the EGFR/PI3K/Akt pathway.Bosn J Basic Med Sci. 2019; 19: 52-59
- miR-452 Reverses Abnormal Glycosylation Modification of ERalpha and Estrogen Resistance in TNBC (Triple-Negative Breast Cancer) Through Targeting UGT1A1.Front Oncol. 2020; 10: 1509
- miR-31-5p may enhance the efficacy of chemotherapy with Taxol and cisplatin in TNBC.Exp Ther Med. 2020; 19: 375-383
- MiR-214-3p regulates the viability, invasion, migration and EMT of TNBC cells by targeting ST6GAL1.Cytotechnology. 2019; 71: 1155-1165
- lncRNA MIR503HG inhibits cell proliferation and promotes apoptosis in TNBC cells via the miR-224-5p/HOXA9 axis.Mol Ther Oncolytics. 2021; 21: 62-73
- Novel prognostic and predictive microRNA targets for triple-negative breast cancer.FASEB J. 2018;
- Quantification of miRNA-mRNA interactions.PLoS One. 2012; 7: e30766
- Long Non-Coding RNA MEG3 Modifies Cell-Cycle, Migration, Invasion, and Proliferation Through AKAP12 by Sponging miR-29c in Meningioma Cells.Front Oncol. 2020; 10537763
- Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression.Sci Rep. 2018; 8: 2098
- circCELSR1 (hsa_circ_0063809) contributes to paclitaxel resistance of ovarian cancer cells by regulating FOXR2 expression via miR-1252.Mol Ther Nucleic Acids. 2020; 19: 718-730
- ceRNA cross-talk in cancer: when ce-bling rivalries go awry.Cancer Discov. 2013; 3: 1113-1121
- The Novel Circular RNA Circ-PGAP3 promotes the proliferation and invasion of triple negative breast cancer by Regulating the miR-330-3p/Myc Axis.Onco Targets Ther. 2020; 13: 10149-10159
- Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation.Nat Genet. 2002; 30: 363-364
- A-kinase anchor protein 12 (AKAP12) inhibits cell migration in breast cancer.Exp Mol Pathol. 2018; 105: 364-370
Article info
Publication history
Published online: November 19, 2022
Accepted:
November 16,
2022
Received in revised form:
October 14,
2022
Received:
February 21,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
