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Published on: March 30, 2019
Circular RNA circCCDC85A inhibits breast cancer progression via acting as a miR-550a-5p sponge to enhance MOB1A
Lingjiao Meng1,2, Sheng Chang1, Yang Sang3
1Tumor Research Institute, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, People's Republic of China.
Background:
A growing body of evidence indicates that abnormal expression of circular RNAs (circRNAs) plays a crucial role by acting as molecular sponges of microRNAs (miRNAs) in various diseases, including cancer. In this study, we explored whether circCCDC85A could function as a miR-550a-5p sponge and influence breast cancer progression.
Methods:
We detected the expression of circCCDC85A in breast cancer tissues and cells using fluorescence in situ hybridization (FISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). CCK-8 and colony formation assay were used to detect the proliferative ability of breast cancer cells. Wound healing assay and transwell migration and invasion assays were used to detect the migrative and invasive abilities of breast cancer cells. We also examined the interactions between circCCDC85A and miR-550a-5p using FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Moreover, we performed luciferase reporter assay, qRT-PCR, and Western blot to confirm the direct targeting of miR-550a-5p to MOB1A.
Results:
The expression of circCCDC85A in breast cancer tissues was obviously lower than that in normal breast tissues. Over-expression of circCCDC85A substantially inhibited the proliferative, migrative, and invasive ability of breast cancer cells, while knocking down of circCCDC85A enhanced the aforementioned properties of breast cancer cells. Moreover, enforced expression of circCCDC85A inhibits the oncogenic activity of miR-550a-5p and increases the expression of MOB1A targeted by miR-550a-5p. Further molecular mechanism research showed that circCCDC85A may act as a molecular sponge for miR-550a-5p, thus restoring miR-550a-5p-mediated targeting repression of tumor suppressor MOB1A in breast cancer cells.
Conclusion:
Our findings provide novel evidence that circCCDC85A inhibits the progression of breast cancer by functioning as a molecular sponge of miR-550a-5p to enhance MOB1A expression.
Insights
Circular RNA CCDC85A (circCCDC85A) acts as a tumor suppressor in breast cancer by sponging miR-550a-5p. This interaction restores MOB1A expression, inhibiting cancer progression and proliferation.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in disease, including cancer, often by regulating microRNAs (miRNAs).
- Aberrant circRNA expression is implicated in various pathologies, necessitating investigation into specific circRNAs like circCCDC85A in cancer development.
Purpose of the Study:
- To investigate the role of circCCDC85A as a potential molecular sponge for miR-550a-5p.
- To determine the impact of circCCDC85A on breast cancer progression, proliferation, migration, and invasion.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) for circCCDC85A expression analysis.
- Cell proliferation, migration, and invasion assays (CCK-8, colony formation, wound healing, Transwell) to assess functional effects.
- Luciferase reporter assays, RNA-binding protein immunoprecipitation (RIP), and Western blot to elucidate molecular interactions and mechanisms.
Main Results:
- circCCDC85A expression was significantly lower in breast cancer tissues compared to normal tissues.
- Overexpression of circCCDC85A suppressed breast cancer cell proliferation, migration, and invasion, while knockdown enhanced these properties.
- circCCDC85A functioned as a molecular sponge for miR-550a-5p, leading to increased expression of MOB1A, a target of miR-550a-5p.
Conclusions:
- circCCDC85A acts as a tumor suppressor in breast cancer by sponging miR-550a-5p.
- This sponging activity enhances MOB1A expression, thereby inhibiting breast cancer progression.
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