Title:Role of miRNA-99a-5p in Modulating the Function of Hepatocellular
Carcinoma Cells: Bioinformatics Analysis and In Vitro Assay
Volume: 23
Issue: 6
Author(s): Jia-Ning Zhang, Feng Wei, Bin Bin Zheng, Liang Tang*Feng-Yuan Chen*
Affiliation:
- Department of Pancreatic-Biliary Surgery,
Changzheng Hospital, Second Military Medical University, Shanghai, China
- Department of Gastroenterology,
Shanghai Punan Hospital of Pudong New District, Shanghai, China
- Department of Gastroenterology, Punan Branch
of Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Keywords:
MiRNA-99a-5p, prognosis, proliferation, liver cancer, targeted therapy, hepatobiliary.
Abstract:
Aim: This study aimed to investigate the biological functions of miRNAs in hepatobiliary
tumors as the focus of targeted therapy research.
Background: Hepatobiliary tumors are among the leading causes of cancer-related deaths worldwide.
Many microRNAs (miRNAs) play an important regulatory role in tumor progression. Our study aims
to explore some biologically functional miRNAs from different datasets of hepatobiliary tumors for
disease diagnosis or treatment.
Objective: In this study, we tried to filter out differentially expressed miRNAs in different tumor datasets
from the GEO database.
Methods: In this study, we first perform analyses in different GEO data sets. After taking the intersection,
the initial scope is limited to several differential RNAs. Then, combined with the existing research
results from Kaplan-Meier survival analysis and literature, the candidate molecule was finally
identified to be studied. Furthermore, the biological characteristics analysis of the candidate molecule
was performed on the basis of Cancermirnome online tool, including expression levels in tumors,
KEGG and GO analysis, ROC analysis, and target gene prediction. Furthermore, the effect of the candidate
molecule on the biological functions of liver cancer was verified by In Vitro assay.
Results: The preliminary analysis of bioinformatics shows that 16 differentially expressed miRNAs
may play an important role in HCC or ICC. Ultimately, we identified miRNA-99a-5p as the only molecule
to study. The results showed that miRNA-99a-5p is abnormally expressed in many tumors, and
in liver cancer, its level of expression in tumor tissue is significantly lower than that in normal tissue.
Then, the KEGG and GO analysis found that it functions in multiple pathways. At the same time, the
ROC analysis found that it showed great potential for prognostic prediction in HCC and we also predicted
that RUNDC3B is the most likely target to which it binds. Finally, the experimental results of
overexpression and knockdown confirmed that miRNA-99a-5p could inhibit cell proliferation in HCC,
which also suggested that it may be an important tumor suppressor in HCC.
Conclusion: MiRNA-99a-5p was negatively correlated with HCC progression and could act as a novel
therapeutic target for HCC.
