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circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a
Rongfang He1,2,3, Peng Liu4, Xiaoming Xie4
1The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Backgroud:
Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in triple negative breast cancer (TNBC) is largely unknown.
Methods:
We performed circRNA microarrays to identify circRNAs that are aberrantly expressed in TNBC cell lines. Expression levels of a significantly upregulated circRNA, circGFRA1, was detected by quantitative real-time PCR (qRT-PCR) in TNBC cell lines and tissues. Kaplan-Meier survival analysis was used to explore the significance of circGFRA1 in clinical prognosis. Then, we examined the functions of circGFRA1 in TNBC by cell proliferation, apoptosis and mouse xenograft assay. In addition, luciferase assay was used to explore the miRNA sponge function of circGFRA1 in TNBC.
Results:
Microarray analysis and qRT-PCR verified a circRNA termed circGFRA1 that was upregulated in TNBC. Kaplan-Meier survival analysis showed that upregulated circGFRA1 was correlated with poorer survival. Knockdown of circGFRA1 inhibited proliferation and promoted apoptosis in TNBC. Via luciferase reporter assays, circGFRA1 and GFRA1 was observed to directly bind to miR-34a. Subsequent experiments showed that circGFRA1 and GFRA1 regulated the expression of each other by sponging miR-34a.
Conclusions:
Taken together, we conclude that circGFRA1 may function as a competing endogenous RNA (ceRNA) to regulate GFRA1 expression through sponging miR-34a to exert regulatory functions in TNBC. circGFRA1 may be a diagnostic biomarker and potential target for TNBC therapy.
Insights
Circular RNA circGFRA1 is upregulated in triple-negative breast cancer (TNBC) and linked to poor prognosis. It acts as a ceRNA by sponging miR-34a, regulating GFRA1, and may serve as a diagnostic biomarker and therapeutic target for TNBC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in tumorigenesis, but their role in triple-negative breast cancer (TNBC) remains unclear.
- This study investigates the function of circRNAs in TNBC development and progression.
Purpose of the Study:
- To identify aberrantly expressed circRNAs in TNBC.
- To elucidate the functional role of circGFRA1 in TNBC.
- To explore circGFRA1 as a potential diagnostic biomarker and therapeutic target for TNBC.
Main Methods:
- CircRNA microarrays and quantitative real-time PCR (qRT-PCR) were used to identify and quantify circGFRA1 expression in TNBC cell lines and tissues.
- Kaplan-Meier survival analysis assessed the clinical significance of circGFRA1.
- Cell proliferation, apoptosis assays, and mouse xenograft models were employed to investigate circGFRA1 function.
- Luciferase reporter assays were performed to determine the miRNA sponge activity of circGFRA1.
Main Results:
- CircGFRA1 was significantly upregulated in TNBC tissues and cell lines.
- High circGFRA1 expression correlated with poorer patient survival.
- Knockdown of circGFRA1 inhibited TNBC cell proliferation and induced apoptosis.
- CircGFRA1 directly binds to miR-34a, acting as a competing endogenous RNA (ceRNA) to regulate GFRA1 expression.
Conclusions:
- CircGFRA1 functions as a ceRNA by sponging miR-34a, thereby regulating GFRA1 expression in TNBC.
- CircGFRA1 holds potential as a diagnostic biomarker and therapeutic target for TNBC.