# m6A modification of lncRNA PHKA1‐AS1 enhances Actinin Alpha 4 stability and promotes non‐small cell lung cancer metastasis

## TL;DR

This study shows how a specific long noncoding RNA, PHKA1-AS1, promotes non-small cell lung cancer metastasis by stabilizing a known oncogene.

## Contribution

The novel finding is that m6A modification of PHKA1-AS1 stabilizes ACTN4, promoting NSCLC progression.

## Key findings

- High m6A modification increases PHKA1-AS1 expression in NSCLC.
- PHKA1-AS1 stabilizes ACTN4 by inhibiting its ubiquitination degradation.
- PHKA1-AS1 promotes NSCLC proliferation and metastasis in vitro and in vivo.

## Abstract

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non‐small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1‐AS1) in the progression of NSCLC were explored. The increased level of N6‐methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1‐AS1. Subsequently, high‐expressed PHKA1‐AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1‐AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1‐AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1‐AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

m6A‐mediated lncRNA PHKA1‐AS1 promotes proliferation and metastasis of NSCLC via increasing ACTN4 stability. Increased m6A modification of lncRNA PHKA1‐AS1 enhanced its expression in NSCLC, which in turn regulated the expression of epithelial‒mesenchymal transition‐related proteins, leading to NSCLC metastasis. Additionally, high levels of PHKA1‐AS1 could bind to the oncogene ACTN4, inhibiting its ubiquitination degradation and enhancing its protein stability, thus promoting NSCLC progression and metastasis.