# Anoectochilusroxburghii extract down-regulates METTL3 to reduce RNA m6A on WNT pathway and inhibit melanoma cancer cell metastasis

**Authors:** Yingyi Ye, Yazhi Tian, Jinchun Chen, Jingjun Zhao

PMC · DOI: 10.7150/jca.92212 · 2024-08-13

## TL;DR

A plant extract reduces melanoma cell spread by lowering METTL3, which affects RNA modifications and the WNT pathway.

## Contribution

The study reveals a novel mechanism by which Anoectochilus roxburghii extract inhibits melanoma metastasis through METTL3 downregulation.

## Key findings

- Anoectochilus roxburghii extract downregulates METTL3 in melanoma cells.
- Reduced METTL3 lowers RNA m6A on UCK2 mRNA, leading to its degradation.
- This process suppresses the Wnt/β-catenin pathway, inhibiting melanoma progression.

## Abstract

Characterized by high invasiveness and expansive growth, melanoma progression is intricately regulated, with RNA m6A modifications playing a pivotal role. Among these regulators, METTL3 modulates the migratory capabilities of melanoma cells, specifically by modifying the RNA m6A of UCK2. The extract of Anoectochilusroxburghii, a plant known for its broad-spectrum antitumour properties, has been shown to effectively curb the invasion and migration of melanoma cells and impede tumour growth. The primary mechanism involves the downregulation of METTL3 expression. By doing so, the Anoectochilus roxburghii extract reduces the m6A level on the mRNA of UCK2, accelerating UCK2 mRNA degradation and, consequently, decreasing UCK2 expression. This process, in turn, suppresses gene expression within the Wnt/β-catenin pathway, contributing to its antimelanoma effects.

## Linked entities

- **Genes:** METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56339], UCK2 (uridine-cytidine kinase 2) [NCBI Gene 7371]
- **Diseases:** melanoma (MONDO:0005105)

## Full-text entities

- **Genes:** METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56339] {aka IME4, M6A, MT-A70, Spo8, hMETTL3}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, UCK2 (uridine-cytidine kinase 2) [NCBI Gene 7371] {aka TSA903, UK, UMPK}
- **Diseases:** melanoma (MESH:D008545), metastasis (MESH:D009362), melanoma cancer (MESH:D009369)
- **Chemicals:** m6A (MESH:C005955), Anoectochilusroxburghii extract (-)
- **Species:** Anoectochilus roxburghii (species) [taxon 569774]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11375548/full.md

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Source: https://tomesphere.com/paper/PMC11375548