# Circular RNA circCD44 targets methyltransferase‐like 3/homeobox containing 1 to facilitate esophageal squamous cell carcinoma progression

## TL;DR

This study shows that a circular RNA called circCD44 helps esophageal cancer grow by working with METTL3 to increase HMBOX1 protein levels.

## Contribution

The novel finding is that circCD44 promotes ESCC progression via METTL3-mediated m6A modification of HMBOX1 mRNA.

## Key findings

- circCD44 and HMBOX1 are overexpressed in ESCC cell lines and promote cancer cell proliferation and invasion.
- METTL3 binds to circCD44 and HMBOX1 mRNA, increasing HMBOX1 protein through m6A modification.
- Knockdown of METTL3 or HMBOX1 reduces the oncogenic effects of circCD44 in ESCC models.

## Abstract

Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal malignancy with unclear functional mechanisms of circular RNAs. This study focused on investigating the role of circCD44 in ESCC progression. The expression of circCD44 and homeobox containing 1 (HMBOX1) was found to be elevated in ESCC cell lines. The overexpression of circCD44 or HMBOX1 enhanced proliferation and invasion, while inhibiting apoptosis in ESCC cells, whereas knockdown of these genes had inverse effects. METTL3 was observed to bind to circCD44 and HMBOX1 mRNA, promoting m6A modification in HMBOX1 mRNA and subsequent HMBOX1 protein expression. Knockdown of METTL3 or HMBOX1 attenuated the oncogenic effects of circCD44 overexpression both in vitro and in vivo. These findings suggest that circCD44 promotes ESCC progression by facilitating HMBOX1 mRNA m6A modification and protein expression through METTL3 binding, providing insights into the molecular mechanisms underlying ESCC pathogenesis.