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miR-18a-5p Targets FBP1 to Promote Proliferation, Migration, and Invasion of Liver Cancer Cells and Inhibit Cell

Shan Gao¹, Dongjie Zhu¹, Jian Zhu¹

¹Department of General Surgery, The First People's Hospital of Yuhang District, Hangzhou, Zhejiang 311100, China.

Computational and Mathematical Methods in Medicine

|July 5, 2021

Abstract:

Liver cancer is one of the most aggressive malignant tumors. It is significant to understand the molecular mechanism of liver cancer cells to develop new treatment plans. Studies have identified that FBP1 serves as a cancer inhibitor gene. To research the effect mechanism of FBP1 in liver cancer cells, bioinformatics analysis was performed to study its expression in liver cancer tissue. Survival analysis was also performed. Moreover, starBase database was applied to predict upstream regulatory genes of FBP1. Dual-luciferase assay was performed to testify their targeted relationship. The mRNA and protein expression levels of FBP1 in liver cancer cells were detected by qRT-PCR and western blot, respectively. Cell viability was analyzed by CCK-8 assay. The migratory and invasive abilities of cells were analyzed by Transwell assay. The apoptosis of liver cancer cells was detected by flow cytometry. The results showed that the expression of FBP1 was downregulated in liver cancer tissue and cells. FBP1 low expression was correlated with the poor prognosis of patients. miR-18a-5p could inhibit FBP1 expression. Overexpression of FBP1 could inhibit the progression of liver cancer cells and promote cell apoptosis. Overexpressing miR-18a-5p could promote the progression of liver cancer cells and inhibit cell apoptosis. However, overexpressing FBP1 simultaneously could reverse the effect. miR-18a-5p and FBP1 are expected to be candidates for liver cancer treatment.

Insights

FBP1 acts as a tumor suppressor in liver cancer, with its low expression linked to poor prognosis. Restoring FBP1 levels inhibits cancer progression and promotes apoptosis, offering potential therapeutic strategies.

Area of Science:

Oncology
Molecular Biology
Biochemistry

Background:

Liver cancer is an aggressive malignancy requiring novel therapeutic targets.
Fructose-1,6-bisphosphatase 1 (FBP1) is identified as a potential tumor suppressor gene.
Understanding FBP1's role in liver cancer is crucial for developing effective treatment plans.

Purpose of the Study:

To investigate the molecular mechanism and therapeutic potential of FBP1 in liver cancer.
To analyze the expression patterns and prognostic significance of FBP1 in liver cancer.
To elucidate the regulatory relationship between miR-18a-5p and FBP1.

Main Methods:

Bioinformatics analysis and survival analysis of FBP1 expression in liver cancer tissues.
Prediction and validation of upstream regulatory genes (miR-18a-5p) using starBase and dual-luciferase assays.
Quantitative real-time PCR (qRT-PCR), Western blot, CCK-8, Transwell, and flow cytometry assays to assess FBP1's functional impact on liver cancer cells.

Main Results:

FBP1 expression was significantly downregulated in liver cancer tissues and cells, correlating with poor patient prognosis.
miR-18a-5p was identified as a negative regulator of FBP1 expression.
Overexpression of FBP1 inhibited liver cancer cell viability, migration, and invasion while promoting apoptosis; conversely, miR-18a-5p promoted cancer progression and inhibited apoptosis, effects reversed by FBP1 co-expression.

Conclusions:

FBP1 functions as a tumor suppressor in liver cancer by inhibiting cell progression and promoting apoptosis.
The miR-18a-5p/FBP1 axis plays a critical role in liver cancer development.
Both miR-18a-5p and FBP1 represent promising therapeutic targets for liver cancer treatment.

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