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A circular RNA, circSMARCA5, inhibits prostate cancer proliferative, migrative, and invasive capabilities via the miR-181b-5p/miR-17-3p-TIMP3 axis
- Source :
- Aging (Albany NY)
- Publication Year :
- 2021
- Publisher :
- Impact Journals, 2021.
-
Abstract
- SMARCA5 (circSMARCA5) is involved in the occurrence of different cancers, but its role in prostate cancer carcinogenesis and metastatic transformation remains elusive. Thus, we evaluated the circSMARCA5 functional relevance in prostate cancer and its associated molecular mechanism. First, circSMARCA5 expression and function in this cancer were evaluated. To determine the miR-181b-5p/miR-17-3p target and clarify how circSMARCA5 regulates the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis, RNA immunoprecipitation, biotin-coupled microRNA capture, luciferase reporter, Western blot, and quantitative real-time PCR assays were employed. In primary and metastatic prostate cancer tissues, circSMARCA5 was significantly downregulated compared with normal controls. Functionally, circSMARCA5 exhibited a suppressive effect on prostate cancer cells' metastasis and growth. At the molecular level, circSMARCA5 could affect the tissue inhibitor of metalloproteinases 3 (TIMP3) expression through miR-181b-5p or miR-17-3p interactions. Moreover, lysine acetyltransferase 5 (KAT5) induced circSMARCA5 biogenesis and regulated the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis. These results suggested that targeting circSMARCA5-miR-181b-5p-TIMP3 and circSMARCA5-miR-17-3p-TIMP3 axis might be a novel therapeutic strategy for prostate cancer.
- Subjects :
- Male
Aging
TIMP3
Chromosomal Proteins, Non-Histone
Mice, Nude
Biology
medicine.disease_cause
Metastasis
Prostate cancer
Mice
Western blot
Circular RNA
Cell Movement
circSMARCA5
Cell Line, Tumor
microRNA
medicine
Animals
Humans
Neoplasm Invasiveness
Cell Proliferation
Lysine Acetyltransferase 5
Adenosine Triphosphatases
Tissue Inhibitor of Metalloproteinase-3
medicine.diagnostic_test
miR-17-3p
miR-181b-5p
Cancer
Prostatic Neoplasms
Cell Biology
RNA, Circular
medicine.disease
prostate cancer
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
MicroRNAs
Cancer research
Carcinogenesis
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 19454589
- Volume :
- 13
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- Aging (Albany NY)
- Accession number :
- edsair.doi.dedup.....f78d212e38ae2354a8cb61e6162eae39