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circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in
Genwen Chen1, Yanting Shi2, Mengmeng Liu1
1Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
Abstract:
Noncoding RNAs plays an important role in hepatocellular carcinoma (HCC). Here, we show that miR-124 was downregulated in HCC tissues and that the ectopic expression of miR-124 inhibited the proliferation and migration of HCC cells. We proposed that aquaporin 3 (AQP3) is a direct target of miR-124. AQP3 was upregulated in HCC tissues and inversely correlated with miR-124 expression. The overexpression of miR-124 decreased AQP3 expression. Indeed, AQP3 overexpression promoted cell proliferation and migration, whereas miR-124 knockdown suppressed cell proliferation and migration. Furthermore, we found that circular RNA HIPK3 (circHIPK3) acted as a miR-124 sponge and regulated the expression of the miR-124 target gene AQP3. circHIPK3 was upregulated in HCC tissues and positively correlated with AQP3 expression. Thus, silencing circHIPK3 inhibited cell proliferation and migration by downregulating AQP3 expression. Moreover, miR-124 inhibition rescued circHIPK3 knockdown induced reduction in cell proliferation and migration, as well as AQP3 expression. In vivo experiments also confirmed that circHIPK3 regulated xenograft tumor growth via the miR-124-AQP3 axis. These observations indicate a possible novel therapeutic strategy involving circular RNAs in HCC.
Insights
MicroRNA-124 (miR-124) suppresses hepatocellular carcinoma (HCC) growth by targeting aquaporin 3 (AQP3). Circular RNA HIPK3 (circHIPK3) exacerbates HCC by sponging miR-124, promoting AQP3 expression and tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- RNA Biology
Background:
- Noncoding RNAs significantly influence hepatocellular carcinoma (HCC) development.
- Dysregulation of microRNAs and circular RNAs is implicated in various cancers, including HCC.
Purpose of the Study:
- To investigate the role of microRNA-124 (miR-124) in HCC.
- To identify the molecular targets of miR-124 in HCC.
- To explore the function of circular RNA HIPK3 (circHIPK3) in HCC progression and its interaction with miR-124.
Main Methods:
- Quantitative real-time PCR to assess miR-124, aquaporin 3 (AQP3), and circHIPK3 expression in HCC tissues and cells.
- Cell proliferation and migration assays (e.g., MTT, Transwell).
- Western blotting to detect protein levels.
- Luciferase reporter assays to confirm direct targeting.
- In vivo xenograft tumor models in mice.
Main Results:
- miR-124 was downregulated in HCC tissues and inhibited HCC cell proliferation and migration.
- AQP3 was identified as a direct target of miR-124, with its expression upregulated in HCC and inversely correlated with miR-124.
- circHIPK3 acted as a molecular sponge for miR-124, leading to increased AQP3 expression and promoting HCC cell proliferation, migration, and tumor growth in vivo.
- Silencing circHIPK3 or overexpressing miR-124 inhibited HCC progression, while miR-124 inhibition rescued the effects of circHIPK3 knockdown.
Conclusions:
- The miR-124/AQP3 axis plays a critical role in HCC progression.
- circHIPK3 promotes HCC by sponging miR-124 and upregulating AQP3 expression.
- Targeting the circHIPK3/miR-124/AQP3 pathway represents a potential therapeutic strategy for HCC.
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