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Published on: April 6, 2012
Long noncoding RNA CCDC183-AS1 depletion represses breast cancer cell proliferation, colony formation, and motility
Tao Liu1, Limin Zhou1, Lianbo Zhang2
1Department of Second Breast Surgery, Jilin Cancer Hospital, Changchun, 130012, China.
Abstract:
Many studies have illustrated the significance of long noncoding RNAs in oncogenesis and promotion of breast cancer (BC). However, the biological roles of CCDC183 antisense RNA 1 (CCDC183-AS1) in BC have rarely been characterized. Thus, we explored whether CCDC183-AS1 is involved in the malignancy of BC and elucidated the possible underlying mechanisms. Our data confirmed elevated CCDC183-AS1 expression in BC, which was associated with poor clinical outcomes. Functionally, knocking down CCDC183-AS1 hampered cell proliferation, colony formation, migration, and invasion in BC. Additionally, the absence of CCDC183-AS1 restrained tumor growth in vivo. Mechanistically, CCDC183-AS1 executed as a competitive endogenous RNA in BC cells by decoying microRNA-3918 (miR-3918) and consequently overexpressing fibroblast growth factor receptor 1 (FGFR1). Furthermore, functional rescue experiments confirmed that inactivation of the miR-3918/FGFR1 regulatory axis by inhibiting miR-3918 or increasing FGFR1 expression could abrogate the CCDC183-AS1 ablation-mediated repressive effects in BC cells. In summary, CCDC183-AS1 deteriorates the malignancy of BC cells by controlling miR-3918/FGFR1 regulatory axis. We believe that our study can deepen our understanding of BC etiology and contribute to an improvement in treatment choices.
Insights
Long noncoding RNA CCDC183-AS1 promotes breast cancer (BC) malignancy by regulating the miR-3918/FGFR1 axis. Targeting CCDC183-AS1 may offer new therapeutic strategies for BC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) play crucial roles in cancer development.
- The specific role of CCDC183 antisense RNA 1 (CCDC183-AS1) in breast cancer (BC) remains largely uncharacterized.
Purpose of the Study:
- To investigate the involvement of CCDC183-AS1 in BC malignancy.
- To elucidate the underlying molecular mechanisms of CCDC183-AS1 in BC.
Main Methods:
- Quantitative real-time PCR to measure CCDC183-AS1 expression.
- Cell proliferation, colony formation, migration, and invasion assays.
- In vivo tumor growth experiments.
- MicroRNA (miRNA) and Western blot analyses to assess the regulatory axis.
Main Results:
- CCDC183-AS1 expression was significantly elevated in BC tissues and correlated with poor clinical outcomes.
- Knockdown of CCDC183-AS1 inhibited BC cell proliferation, migration, invasion, and tumor growth in vivo.
- CCDC183-AS1 acted as a competing endogenous RNA by sponging miR-3918, leading to fibroblast growth factor receptor 1 (FGFR1) overexpression.
- Inhibition of miR-3918 or overexpression of FGFR1 rescued the suppressive effects of CCDC183-AS1 knockdown.
Conclusions:
- CCDC183-AS1 promotes BC cell malignancy through the CCDC183-AS1/miR-3918/FGFR1 axis.
- CCDC183-AS1 represents a potential therapeutic target for breast cancer treatment.
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