Ginsenoside Rh2 reduces m6A RNA methylation in cancer via the KIF26B-SRF positive feedback loop

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Ginsenoside Rh2 exhibits potential tumor-suppressive effects, but its underlying mechanisms are complex.
• N6-methyladenosine (m6A) RNA methylation is frequently dysregulated in various cancers.
• This study investigates the regulatory role of ginsenoside Rh2 in cancer m6A RNA methylation.

Purpose of the Study:

• To explore the effect of ginsenoside Rh2 on m6A RNA methylation in cancer.
• To elucidate the molecular mechanisms by which ginsenoside Rh2 influences cancer progression.

Main Methods:

• Assessed total and gene-specific m6A RNA levels using m6A RNA quantification and m6A RNA immunoprecipitation quantitative PCR (RIP-qPCR).
• Investigated protein interactions and cellular localization via co-immunoprecipitation, fractionation western blotting, and immunofluorescence staining.
• Examined transcriptional regulation using quantitative reverse transcription PCR (qRT-PCR), dual-luciferase assays, and chromatin immunoprecipitation qPCR (ChIP-qPCR).

Main Results:

• Ginsenoside Rh2 dose-dependently reduced m6A RNA methylation and KIF26B expression in certain cancers.
• KIF26B facilitated the nuclear localization of ZC3H13 and CBLL1, thereby increasing m6A RNA methylation.
• The KIF26B-SRF axis formed a positive feedback loop promoting cancer cell proliferation and growth in vitro and in vivo.

Conclusions:

• Ginsenoside Rh2 suppresses cancer cell proliferation by decreasing m6A RNA methylation via KIF26B downregulation.
• KIF26B enhances m6A RNA methylation by promoting the nuclear distribution of ZC3H13 and CBLL1.
• The KIF26B-SRF feedback loop is a key driver of tumor growth.