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Circ_0067835 sponges miR-324-5p to induce HMGA1 expression in endometrial carcinoma cells
Yun Liu1, Yue Chang1, Yixuan Cai1
1Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China.
Abstract:
Endometrial cancer is a common gynaecological malignant tumour among women across the world. Circular RNAs (circRNAs) are a novel kind of non-coding RNAs, and they can play a crucial role in multiple cancers. Nevertheless, the mechanisms of circRNAs in regulating gene expression in endometrial cancer are still unclear. Here, our work sought to focus on the role that circ_0067835 exert in progression and development of endometrial cancer cells. We observed circ_0067835 was markedly elevated in endometrial cancer. Then, changes in endometrial cancer cell (RL95-2 and HEC-1B) function were determined after circ_0067835 knockdown. Loss-of-functional assays revealed that circ_0067835 down-regulation significantly repressed RL95-1 and HEC-1B cell proliferation, migration and invasion. Bioinformatics analysis, luciferase reporter experiment and RNA pull-down assay were employed to predict and validate circ_0067835 can bind to miR-324-5p. Increase in miR-324-5p remarkably depressed the proliferation, migration and invasion of endometrial cancer cells via inhibiting high mobility group A1 (HMGA1). HMGA1 is identified as a vital prognostic biomarker in endometrial cancer. Currently, we reported circ_0067835 was positively correlated with HMGA1 in endometrial cancer. We implied that circ_0067835 was capable of sponging miR-324-5p and inducing its downstream target HMGA1 in vitro and in vivo. In conclusion, circ_0067835 can compete with miR-324-5p, resulting in HMGA1 up-regulation, and therefore induce the development of endometrial cancer.
Insights
Circular RNAs (circRNAs) like circ_0067835 promote endometrial cancer by sponging miR-324-5p, leading to increased HMGA1 expression and tumor progression. Targeting this pathway may offer new therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Endometrial cancer is a prevalent gynecological malignancy worldwide.
- Circular RNAs (circRNAs) are implicated in various cancers, but their specific roles in endometrial cancer remain largely unknown.
- Understanding the regulatory mechanisms of circRNAs is crucial for developing novel diagnostic and therapeutic approaches.
Purpose of the Study:
- To investigate the role of circ_0067835 in the progression and development of endometrial cancer cells.
- To elucidate the molecular mechanism by which circ_0067835 influences endometrial cancer growth.
- To identify potential therapeutic targets within the circRNA-miRNA-mRNA axis.
Main Methods:
- Quantitative real-time PCR to measure circ_0067835 expression levels in endometrial cancer tissues and cell lines.
- Loss-of-function assays (siRNA-mediated knockdown) to assess the impact of circ_0067835 on cell proliferation, migration, and invasion.
- Bioinformatics analysis, luciferase reporter assays, and RNA pull-down assays to validate the interaction between circ_0067835, miR-324-5p, and high mobility group A1 (HMGA1).
Main Results:
- Circ_0067835 expression was significantly elevated in endometrial cancer tissues and cell lines.
- Knockdown of circ_0067835 markedly repressed proliferation, migration, and invasion of endometrial cancer cells (RL95-2 and HEC-1B).
- Circ_0067835 was found to directly bind to miR-324-5p, acting as a molecular sponge. Upregulation of miR-324-5p inhibited endometrial cancer cell proliferation, migration, and invasion by suppressing HMGA1. Circ_0067835 positively correlated with HMGA1 expression.
Conclusions:
- Circ_0067835 acts as an oncogenic circRNA in endometrial cancer by sponging miR-324-5p and consequently upregulating its downstream target, HMGA1.
- The circ_0067835/miR-324-5p/HMGA1 axis plays a critical role in promoting endometrial cancer progression.
- Circ_0067835 may serve as a potential diagnostic biomarker and therapeutic target for endometrial cancer.
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