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Knockdown of circular RNA septin 9 inhibits the malignant progression of breast cancer by reducing the expression of solute carrier family 1 member 5 in a microRNA-149-5p-dependent manner

Authors :
Kunxian Yang
Jianjun Wang
Junyu Cao
Li Li
Source :
Bioengineered, article-version (VoR) Version of Record, Bioengineered, Vol 12, Iss 2, Pp 10624-10637 (2021)
Publication Year :
2021
Publisher :
Informa UK Limited, 2021.

Abstract

Breast cancer (BC) is the most frequently diagnosed cancer in women. Increasing evidence suggests that circular RNA (circRNA) exerts critical functions in BC progression. However, the roles of circRNA septin 9 (circSEPT9) in BC development and the underneath mechanism remain largely unclear so far. In this work, the RNA levels of circSEPT9, microRNA-149-5p (miR-149-5p) and solute carrier family 1 member 5 (SLC1A5) were detected by quantitative real-time polymerase chain reaction. Western blot was performed to check protein expression. Glutamine uptake, cell proliferation and cell apoptosis were investigated by glutamine uptake, cell counting kit-8, cell colony formation, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis or DNA content quantitation assay. The interactions of miR-149-5p with circSEPT9 and SLC1A5 were identified by a dual-luciferase reporter assay. Mouse model assay was carried out to analyze the effect of circSEPT9 on tumor formation in vivo. Results showed that circSEPT9 and SLC1A5 expression were significantly upregulated, while miR-149-5p was downregulated in BC tissues and cells as compared with paracancerous normal breast tissues and human normal breast cells. Knockdown of circSEPT9 or SLC1A5 inhibited glutamine uptake and cell proliferation, but induced cell apoptosis in BC cells. SLC1A5 overexpression relieved circSEPT9 silencing-induced repression of BC cell malignancy. In mechanism, circSEPT9 regulated SLC1A5 expression by sponging miR-149-5p. In support, circSEPT9 knockdown led to delayed tumor tumorigenesis in vivo. In summary, these results indicates that circSEPT9 may act an oncogenic role in BC malignant progression by regulating miR-149-5p/SLC1A5 pathway, providing a novel mechanism responsible for BC development.

Details

ISSN :
21655987 and 21655979
Volume :
12
Database :
OpenAIRE
Journal :
Bioengineered
Accession number :
edsair.doi.dedup.....0a04abe2d5bb04d52a6fea83ef491180