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Published on: March 30, 2019
Circular GOLPH3 RNA exerts oncogenic effects in vitro by regulating the miRNA-1299/LIF axis in oral squamous cell
Chen Zou1, Xia Li1, Haigang Wei1
1School of Medicine, Foshan Stomatological Hospital, Foshan University, Foshan, Guangdong, China.
Abstract:
Circular RNAs, which are a novel subclass of noncoding RNAs, are reported to be involved in various biological processes. Aberrant expression of circular RNAs may promote cancer progression. The function of circular GOLPH3 RNA (circGOLPH3) in oral squamous cell carcinoma (OSCC) is unclear. In this study, the circGOLPH3 levels in OSCC cell lines were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function and loss-of-function experiments were performed to evaluate the roles of circGOLPH3 in OSCC. Cell counting kit 8, migration, and invasion assays were performed to determine the functions of circGOLPH3. The mechanism of circGOLPH3 in OSCC was investigated using qRT-PCR, western blotting, luciferase activity, and RNA pull-down analyses. Furthermore, the function of circGOLPH3 in vivo was evaluated. circGOLPH3 derived from GOLPH3 was mainly localized to the cytoplasm and exhibited high stability. The expression of circGOLPH3 was upregulated in OSCC cells. circGOLPH3 promoted the growth of OSCC in vitro and in vivo. Additionally, circGOLPH3 upregulated OSCC cell migration and invasion. Mechanistically, circGOLPH3 functioned as a microRNA sponge and downregulated miR-1299 expression. miR-1299 downregulated the expression of LIF by targeting its 3'-untranslated region. Inhibition of the circGOLPH3/miR-1299/LIF axis suppressed the growth, migration, and invasion of OSCC cells. These findings indicate that the circGOLPH3/miR-1299/LIF axis promotes OSCC cell growth, migration, and invasion and that this axis is a potential therapeutic target for OSCC.
Insights
Circular GOLPH3 RNA (circGOLPH3) promotes oral squamous cell carcinoma (OSCC) growth, migration, and invasion. Targeting the circGOLPH3/miR-1299/LIF pathway may offer a new therapeutic strategy for OSCC.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Circular RNAs (circRNAs) are novel noncoding RNAs implicated in biological processes, with aberrant expression potentially driving cancer progression.
- The specific role of circGOLPH3 in oral squamous cell carcinoma (OSCC) remains largely uncharacterized.
- Understanding circRNA functions is crucial for developing new cancer therapies.
Purpose of the Study:
- To investigate the expression and function of circGOLPH3 in oral squamous cell carcinoma (OSCC).
- To elucidate the underlying molecular mechanism of circGOLPH3 in promoting OSCC progression.
- To evaluate the therapeutic potential of targeting the circGOLPH3 pathway in OSCC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to determine circGOLPH3 expression levels.
- In vitro gain-of-function and loss-of-function experiments using cell counting kit-8, migration, and invasion assays.
- In vivo studies and molecular mechanism investigations including western blotting, luciferase activity, and RNA pull-down assays.
Main Results:
- circGOLPH3 was found to be upregulated in OSCC cells and localized in the cytoplasm with high stability.
- circGOLPH3 significantly promoted OSCC cell growth, migration, and invasion both in vitro and in vivo.
- circGOLPH3 acts as a microRNA sponge for miR-1299, leading to the downregulation of LIF expression via the circGOLPH3/miR-1299/LIF axis.
Conclusions:
- The circGOLPH3/miR-1299/LIF axis plays a critical role in promoting the growth, migration, and invasion of OSCC cells.
- circGOLPH3 functions as an oncogenic circRNA in OSCC by sponging miR-1299 and upregulating LIF.
- This axis represents a promising therapeutic target for the treatment of oral squamous cell carcinoma.
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