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Circ-PRMT5 promotes breast cancer by the miR-509-3p/TCF7L2 axis activating the PI3K/AKT pathway.
- Source :
-
The journal of gene medicine [J Gene Med] 2021 Feb; Vol. 23 (2), pp. e3300. Date of Electronic Publication: 2020 Dec 27. - Publication Year :
- 2021
-
Abstract
- Background: Breast cancer is the most prevalent malignancy occurring in females. In recent years, emerging evidence has suggested that circular RNAs are involved in the development of multiple cancers. Circ-PRMT5 has recently attracted attention as a tumor-promoting circular RNA. In the present study, we focused on exploring the biological effects of circ-PRMT5 in breast cancer.<br />Methods: A quantitative real-time polymerase chain reaction was used to determine the expression of circ-PRMT5 in breast cancer. In vitro experiments, including cell-counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry and tube formation assays, were performed to test the effects of circ-PRMT5 on the cellular progression of breast cancer. Bioinformatic analysis, luciferase reporter, radioimmunoprecipitation and RNA-pull down assays were performed to predict the potential microRNAs interacting with circ-PRMT5 and mRNAs that can be targeted by miR-509-3p.<br />Results: Circ-PRMT5 is up-regulated in breast cancer tissues and cells. Importantly, an elevation of circ-PRMT5 indicates a poor prognosis in patients with breast cancer. Functionally, knockdown of circ-PRMT5 suppresses cell proliferation and angiogenesis and increases cell apoptosis in breast cancer. Mechanistically, we identified that circ-PRMT5 up-regulates TCF7L2 expression by acting as a miR-509-3p sponge. The negative expression correlation between miR-509-3p and circ-PRMT5 or TCF7L2 in clinical tissues was further demonstrated. Rescue assays showed that TCF7L2 overexpression reverses the antitumoral effects of circ-PRMT5 knockdown on breast cancer cell processes. Additionally, we demonstrated that circ-PRMT5 activates the phosphoinositide 3-kinase (PI3K)/AKT pathway by up-regulation of TCF7L2.<br />Conclusions: Overall, our data indicate that the circ-PRMT5/miR-509-3p/TCF7L2 axis can aggravate the malignant character of breast cancer cells by the regulation of the PI3K/AKT pathway.<br /> (© 2020 John Wiley & Sons, Ltd.)
- Subjects :
- Apoptosis
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Knockdown Techniques
Humans
MicroRNAs
Neovascularization, Pathologic
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Transcription Factor 7-Like 2 Protein metabolism
Breast Neoplasms genetics
Breast Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Protein-Arginine N-Methyltransferases genetics
RNA, Circular
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1521-2254
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The journal of gene medicine
- Publication Type :
- Academic Journal
- Accession number :
- 33277756
- Full Text :
- https://doi.org/10.1002/jgm.3300