miR-671-5p Promotes Cell Proliferation, Invasion, and Migration in Hepatocellular Carcinoma through Targeting ALDH2
Xiao Chen1, Jiansheng Luo1, Shengqiang Gao1
1Department of Hepatopancreatobiliary Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, 321000, China.
Abstract:
We explored the mechanism of acetaldehyde dehydrogenase 2 (ALDH2) in modulating cell behaviors in hepatocellular carcinoma (HCC), and provided fresh ideas for targeted treatment of HCC. The target messenger RNA (mRNA) was determined by The Cancer Genome Atlas (TCGA) analysis, and the upstream regulatory gene miRNA was obtained by further analysis. The expression of ALDH2 mRNA and miR-671-5p in HCC cell lines was assayed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and protein expression was assessed by Western blot. The impact of ALDH2 on biological functions of HCC cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing, and Transwell assays. Bioinformatics method was utilized to predict binding site of miR-671-5p and ALDH2, and their targeted relationship was detected by dual-luciferase gene assay, qRT-PCR and Western blot. ALDH2 expression was reduced in HCC tissue and cell lines. ALDH2 worked as a tumor inhibitor in HCC. Overexpressing ALDH2 could hinder proliferation, migration and invasion of HCC cells. miR-671-5p was the upstream regulatory gene of ALDH2, and it presented remarkably high expression in HCC. A negative modulatory relationship existed between miR-671-5p and ALDH2. The rescue experiments further illustrated the effects of the two on the malignant behaviors of HCC cells. Forced expression of miR-671-5p fostered the proliferation, migration and invasion of HCC cells by restraining ALDH2.
Insights
Acetaldehyde dehydrogenase 2 (ALDH2) inhibits hepatocellular carcinoma (HCC) progression. Its downregulation by miR-671-5p promotes HCC cell proliferation, migration, and invasion, offering a potential therapeutic target.
Area of Science:
- Molecular Oncology
- Biochemistry
- Cancer Biology
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited targeted treatment options.
- Understanding the molecular mechanisms regulating HCC cell behavior is crucial for developing effective therapies.
- Acetaldehyde dehydrogenase 2 (ALDH2) is a key enzyme with potential roles in cancer, but its specific function in HCC is not fully elucidated.
Purpose of the Study:
- To investigate the role of acetaldehyde dehydrogenase 2 (ALDH2) in modulating hepatocellular carcinoma (HCC) cell behaviors.
- To identify the upstream regulatory microRNA (miRNA) of ALDH2 in HCC.
- To explore the potential of targeting the ALDH2/miR-671-5p axis for HCC treatment.
Main Methods:
- Bioinformatic analysis (The Cancer Genome Atlas) to identify target mRNA and upstream miRNA.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot to assess gene and protein expression.
- Cellular assays (MTT, wound-healing, Transwell) to evaluate the impact of ALDH2 on HCC cell functions.
- Dual-luciferase reporter assay to confirm the interaction between miR-671-5p and ALDH2.
Main Results:
- ALDH2 expression was significantly reduced in HCC tissues and cell lines, indicating its role as a tumor suppressor.
- Overexpression of ALDH2 inhibited HCC cell proliferation, migration, and invasion.
- miR-671-5p was identified as a direct upstream regulator of ALDH2, with high expression in HCC, and negatively modulated ALDH2 expression.
- Forced expression of miR-671-5p promoted HCC cell malignancy by suppressing ALDH2.
Conclusions:
- ALDH2 functions as a tumor suppressor in hepatocellular carcinoma by inhibiting cell proliferation, migration, and invasion.
- miR-671-5p promotes HCC progression by downregulating ALDH2 expression.
- The miR-671-5p/ALDH2 axis represents a promising therapeutic target for hepatocellular carcinoma treatment.
