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Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids
Published on: August 18, 2023
MicroRNA‑584 prohibits hepatocellular carcinoma cell proliferation and invasion by directly targeting BDNF
Yanan Song1, Guoyu Wang1, Juhua Zhuang1
1Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China.
Abstract:
In recent decades, an increasing number of studies have demonstrated that numerous microRNAs (miRNAs) are dysregulated in hepatocellular carcinoma (HCC); these aberrantly expressed miRNAs are contributing regulators of HCC formation and progression. Thus, revealing the biological roles of miRNAs in HCC may provide novel information on the identification of effective therapeutic targets and valuable diagnosis methods. Herein, reverse transcription‑quantitative PCR was performed to determine the expression profile of miRNA‑584 (miR‑584) in HCC tissues and cell lines. Cell Counting Kit‑8 and cell invasion assays were utilized to evaluate the influence of mIR‑584 overexpression on HCC cell proliferation and invasion, respectively. The present study demonstrated that miR‑584 expression was reduced in HCC tissues and cell lines compared with normal controls. Clinical analysis indicated that decreased miR‑584 expression was significantly associated with tumor size, TNM stage and lymph node metastasis of patients with HCC. Additionally, resumption of miR‑584 expression inhibited proliferation and invasion of HCC cells. Mechanistically, it was demonstrated that miR‑584 can directly interact with the 3'‑untranslated regions of brain‑derived neurotrophic factor (BDNF) mRNA, and reduce its mRNA and protein levels in HCC cells. Furthermore, BDNF was upregulated in HCC tissues, and its level was inversely correlated with miR‑584 expression. Notably, restored BDNF expression antagonized the inhibitory effects of miR‑584 overexpression on HCC cells. In conclusion, miR‑584 may serve tumor‑suppressive roles in HCC by directly targeting BDNF, thus suggesting that miR‑584 may serve as a potential candidate for treatment of patients with this disease.
Insights
MicroRNA-584 (miR-584) is downregulated in hepatocellular carcinoma (HCC), inhibiting tumor growth and spread. Restoring miR-584 may offer a new therapeutic strategy for HCC patients by targeting brain-derived neurotrophic factor (BDNF).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators in hepatocellular carcinoma (HCC) development and progression.
- Dysregulated miRNA expression in HCC presents opportunities for novel therapeutic targets and diagnostic methods.
Purpose of the Study:
- To investigate the expression profile and functional role of miRNA-584 (miR-584) in hepatocellular carcinoma (HCC).
- To elucidate the potential molecular mechanisms underlying miR-584's function in HCC, including its interaction with brain-derived neurotrophic factor (BDNF).
Main Methods:
- Reverse transcription-quantitative PCR (RT-qPCR) to assess miR-584 expression in HCC tissues and cell lines.
- Cell Counting Kit-8 and cell invasion assays to evaluate the impact of miR-584 on HCC cell proliferation and invasion.
- Analysis of miR-584's direct interaction with BDNF mRNA and its effect on BDNF protein levels.
Main Results:
- miR-584 expression was significantly reduced in HCC tissues and cell lines compared to normal controls.
- Decreased miR-584 levels correlated with advanced tumor size, TNM stage, and lymph node metastasis in HCC patients.
- Overexpression of miR-584 suppressed HCC cell proliferation and invasion, and this was mediated by direct targeting of BDNF mRNA.
Conclusions:
- miR-584 exhibits tumor-suppressive functions in HCC by directly targeting and downregulating BDNF.
- miR-584 may serve as a potential therapeutic candidate for hepatocellular carcinoma treatment.
- The miR-584/BDNF axis represents a promising target for HCC therapy and diagnosis.
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