Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in
Dan Fei1, Xiaona Zhang2, Jinxiang Liu3
1Department of Ultrasonographic, China-Japan Union Hospital of Jilin University, Changchun, China.
Background/Aims:
Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism.
Methods:
We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created.
Results:
We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues.
Conclusion:
These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.
Insights
Long non-coding RNA FER1L4 is downregulated in osteosarcoma (OS) and inhibits tumor progression by acting as a competing endogenous RNA (ceRNA) for miR-18a-5p, upregulating PTEN. FER1L4 represents a potential therapeutic target for OS.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Osteosarcoma (OS) is a primary bone malignancy with limited therapeutic options.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer, but the function of FER1L4 in OS is unknown.
Purpose of the Study:
- To investigate the clinical significance and biological function of FER1L4 in osteosarcoma.
- To elucidate the underlying molecular mechanism of FER1L4 in OS progression.
Main Methods:
- Quantitative RT-PCR (qRT-PCR) to assess FER1L4 expression in OS tissues and cell lines.
- In vitro functional assays (proliferation, colony formation, migration, invasion) and in vivo tumor xenografts to evaluate FER1L4's effects.
- Bioinformatics, dual-luciferase reporter assays, and qRT-PCR to identify and confirm FER1L4 targets.
Main Results:
- FER1L4 expression was significantly downregulated in OS tissues and associated with advanced TNM stage, metastasis, and poor survival.
- Upregulation of FER1L4 suppressed OS cell proliferation, colony formation, migration, invasion in vitro, and tumor growth in vivo.
- FER1L4 acted as a competing endogenous RNA (ceRNA) for miR-18a-5p, increasing PTEN expression, which is downregulated in OS.
Conclusions:
- FER1L4 functions as an anti-cancer agent in osteosarcoma by modulating the miR-18a-5p/PTEN axis.
- FER1L4 holds promise as a novel diagnostic biomarker and therapeutic target for osteosarcoma.
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