# Mechanism of N6-methyladenosine (m6A)-mediated upregulation of LINC00958 in the growth of cervical cancer

## TL;DR

This study reveals how a specific RNA modification (m6A) boosts a non-coding RNA (LINC00958) to promote cervical cancer growth through a molecular pathway involving c-MYC and BAG3.

## Contribution

The novel contribution is identifying the m6A-mediated mechanism by which LINC00958 promotes cervical cancer via the c-MYC/BAG3 axis.

## Key findings

- LINC00958 is upregulated in cervical cancer and linked to poor prognosis.
- LINC00958 promotes cancer cell proliferation and suppresses apoptosis through the c-MYC/BAG3 pathway.
- METTL3-mediated m6A modification stabilizes LINC00958, increasing its expression.

## Abstract

Cervical cancer (CC) remains a prominent contributor to cancer mortality amongst women. Long non-coding RNAs (LncRNAs) participate in CC progression. This study probed into the potential mechanism of LINC00958 in CC growth.

LINC00958 expression in CC tissues and cells was determined. The correlation between LINC00958 expression and CC prognosis was analyzed. LINC00958 expression was interfered in CC cells, followed by assessment of CC cell proliferation and apoptosis. An xenograft tumor model was established in nude mice. METTL3, c-MYC, and BAG3 expression was determined. m6A level was quantitatively analyzed, and the level of m6A-modified LINC00958 was detected. The binding of LINC00958 to c-MYC, as well as the binding of c-MYC to BAG3 were confirmed. Functional rescue experiments were designed to verify the effect of METTL3/BAG3 on CC growth.

LINC00958 expression was elevated in CC and correlated with the prognosis and clinicopathological features of CC patients. LINC00958 silencing suppressed CC cell proliferation and facilitated apoptosis in vitro, and repressed tumor growth in vivo. Mechanically, METTL3-mediated m6A modification elevated LINC00958 expression by promoting LINC00958 stability. LINC00958 activated the transcriptional activity of c-MYC, and c-MYC bound to BAG3. METTL3 overexpression or BAG3 overexpression offset the impact of LINC00958 silencing on CC growth.

METTL3-mediated m6A modification elevated LINC00958 expression. LINC00958 enhanced CC cell proliferation but depressed apoptosis via the c-MYC/BAG3 axis.