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Published on: March 30, 2019
CircDDX17 acts as a competing endogenous RNA for miR-605 in breast cancer progression
1Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. qslp1250072@yeah.net.
Objective:
Circular RNAs (circRNAs), a novel class of noncoding RNAs, are reported to be involved in the progression of various cancers. CircDDX17 was reported as a tumour suppressor in colorectal cancer. However, the expression and role of circDDX17 in breast cancer remain unclear.
Patients And Methods:
We used qPCR analysis to reveal the expression levels of circRNAs and miRNAs in breast cancer tissues and cell lines. The target relationship between circRNA and miRNAs was predicted using miRanda and then detected using a Luciferase reporter assay. The effects of circDDX17 and miR-605 on the growth of breast cancer were detected using MTT, colony formation assay and apoptosis analysis.
Results:
In this study, low circDDX17 expression was observed in breast cancer tissues and cell lines. Moreover, circDDX17 expression was inversely associated with the clinicopathological parameters of tumour grade and advanced TNM stage (p<0.05). Functionally, overexpressed circDDX17 inhibited cell proliferation and colony formation and promoted cell apoptosis in breast cancer. Mechanistically, circDDX17 directly bound to miR-605, which functions as an oncogene in breast cancer, and its expression was associated with low overall survival of breast cancer patients. Finally, we found that circDDX17 suppressed cell proliferation by regulating cell cycle-related factors (CDK1 and p21), and the effect was reversed by miR-605 mimics.
Conclusions:
We identified the downregulation of circDDX17 in breast cancer, and circDDX17 acted as a tumour suppressor by inhibiting proliferation and promoting apoptosis through its function as a sponge of miR-605 in breast cancer, indicating that it serves as a potential biomarker and a therapeutic target for breast cancer.
Insights
Circular RNA DDX17 (circDDX17) is downregulated in breast cancer and acts as a tumor suppressor. It inhibits cancer cell growth and promotes apoptosis by sponging miR-605, suggesting potential as a biomarker and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Noncoding RNA Research
Background:
- Circular RNAs (circRNAs) are implicated in cancer progression.
- CircDDX17 previously showed tumor suppressor activity in colorectal cancer.
- The role of circDDX17 in breast cancer remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and function of circDDX17 in breast cancer.
- To elucidate the molecular mechanism underlying circDDX17's role in breast cancer.
- To assess the potential of circDDX17 as a biomarker and therapeutic target.
Main Methods:
- Quantitative PCR (qPCR) for expression analysis.
- Bioinformatic prediction (miRanda) and luciferase reporter assays for miRNA targeting.
- Cell proliferation (MTT, colony formation) and apoptosis assays to determine functional effects.
Main Results:
- CircDDX17 expression is significantly downregulated in breast cancer tissues and cell lines.
- Low circDDX17 expression correlates with higher tumor grade and advanced TNM stage.
- Overexpression of circDDX17 suppresses breast cancer cell proliferation, colony formation, and induces apoptosis.
- CircDDX17 directly targets and inhibits the oncogenic miR-605.
- CircDDX17 regulates cell cycle factors CDK1 and p21, with effects reversed by miR-605.
Conclusions:
- CircDDX17 functions as a tumor suppressor in breast cancer.
- CircDDX17 inhibits proliferation and promotes apoptosis via the circDDX17/miR-605 axis.
- CircDDX17 represents a potential diagnostic biomarker and therapeutic target for breast cancer.
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