Yonsei Med J.  2020 Jun;61(6):460-470. 10.3349/ymj.2020.61.6.460.

MicroRNA-98-5p Inhibits Tumorigenesis of Hepatitis B Virus-Related Hepatocellular Carcinoma by Targeting NF-κB-Inducing Kinase

• Fei X
• Zhang P
• Pan Y
• Liu Y

• KMID: 2502227
• DOI: http://doi.org/10.3349/ymj.2020.61.6.460

Abstract

Purpose
MicroRNAs play key regulatory roles in the tumorigenesis of hepatitis B virus-related hepatocellular carcinoma (HBVHCC). This study aimed to explore the regulatory effects of microRNA-98-5p (miR-98-5p) on the proliferation, migration, invasion, and apoptosis of HBV-HCC cells, as well as the underlying mechanisms involving nuclear factor-κB-inducing kinase (NIK).
Materials and Methods
The expressions of miR-98-5p and NIK in HBV-HCC tissues and cells, and the level of HBV DNA in HBVHCC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, and apoptosis of HBV-HCC cells were analyzed by cell counting kit-8, wound healing, transwell, and flow cytometry assay, respectively. The targeting relationship between miR-98-5p and NIK was predicted by StarBase3.0 and verified by dual-luciferase reporter assay. HBV-HCC xenograft tumor model was constructed in mice to observe the tumor growth in vivo.
Results
The expression of miR-98-5p was declined in HBV-HCC tissues and cells. Overexpression of miR-98-5p markedly reduced the level of HBV DNA; inhibited the proliferation, migration, and invasion; and promoted the apoptosis of HBV-HCC cells. NIK was a target of miR-98-5p. Overexpression of miR-98-5p markedly decreased the protein expression of NIK in MHCC97H-HBV cells. NIK reversed the tumor-suppressing effect of miR-98-5p on HBV-HCC cells. Furthermore, overexpression of miR-98-5p significantly inhibited the xenograft tumor growth and decreased the expression of NIK in mice.
Conclusion
MiR-98-5p inhibits the secretion of HBV, proliferation, migration, and invasion of HBV-HCC cells by targeting NIK.

Keyword

MicroRNA-98-5p; hepatitis B virus-related hepatocellular carcinoma; proliferation; invasion; nuclear factor-κB-inducing kinase