# Inhibition of the long non-coding RNA MALAT1 downregulates MAP2K1, suppressing the progression of hypopharyngeal squamous cell carcinoma

## TL;DR

This study shows that inhibiting the lncRNA MALAT1 reduces cancer progression in hypopharyngeal squamous cell carcinoma by downregulating MAP2K1.

## Contribution

The study identifies MAP2K1 as a novel downstream target of MALAT1 in HSCC and demonstrates its therapeutic potential.

## Key findings

- LncRNA MALAT1 is significantly upregulated in HSCC and linked to poor prognosis.
- Inhibiting MALAT1 suppresses cancer cell proliferation, migration, and tumor growth by downregulating MAP2K1.
- MAP2K1 was validated as a key downstream target through multiple experimental and bioinformatics approaches.

## Abstract

This study aimed to explore the role of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript (lncRNA MALAT1), and its underlying mechanisms in hypopharyngeal squamous cell carcinoma (HSCC). Quantitative real-time PCR (qRT-PCR) was employed to measure lncRNA MALAT1 expression in HSCC and adjacent non-cancerous tissues, along with the expression of the downstream target mitogen-activated protein kinase kinase 1 (MAP2K1). The independent prognostic significance of lncRNA MALAT1 was assessed using Cox regression analysis. Potential downstream targets of MALAT1 were identified through parallel reaction monitoring (PRM) analysis and validated using the TCGA-HNSC database, Western blotting, and immunohistochemistry. CCK-8, flow cytometry, and Transwell assays were conducted to assess the effects of the lncRNA MALAT1/MAP2K1 axis on FaDu cells. Additionally, a nude mouse xenograft model was used to confirm the role of lncRNA MALAT1/MAP2K1 in tumor growth. LncRNA MALAT1 was significantly upregulated in HSCC tissues and closely associated with poor prognosis. Bioinformatics analysis, including PRM screening and TCGA-HNSC data, identified FERMT2, CSNK2A2, and MAP2K1 as potential downstream targets of MALAT1. Validation through qPCR, Western blotting, and immunohistochemistry confirmed MAP2K1 as a downstream target. In vitro and in vivo experiments demonstrated that inhibiting lncRNA MALAT1 suppressed cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT) by downregulating MAP2K1 expression. Additionally, it induced apoptosis, affected the cell cycle, and inhibited tumor growth. Our study uniquely demonstrates that targeting MALAT1 significantly impedes HSCC progression by downregulating its novel downstream target, MAP2K1, offering new insights into potential therapeutic strategies.