HNRNPC promotes progression of non-small cell lung cancer by maintaining TFAP2A mRNA stability

Sep 24, 2026

HNRNPC is an m6A-binding RNA protein overexpressed across cancers, but its specific molecular role in non-small cell lung cancer (NSCLC) remains unclear. This study investigates how HNRNPC regulates NSCLC progression through TFAP2A by combining pan-cancer and LUAD expression mining, RIP-seq/meRIP-qPCR and mRNA stability assays, and differential analysis via immunohistochemistry and functional cellular experiments. Results show HNRNPC preserves TFAP2A mRNA stability, activates the TFAP2A/CTNNB1 axis, promotes EMT, and enhances malignant growth and distant metastasis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

Overview of NSCLC and metastasis

m6A and RNA-binding proteins

HNRNPC in cancer

EMT and metastatic signatures

Liao et al. Cancer Cell International (2025) 25:85 [https://doi.org/10.1186/s12935-025-03660-x](https://doi.org/10.1186/s12935-025-03660-x) Cancer Cell International RESEARCH Open Access HNRNPC promotes progression of non-small cell lung cancer by maintaining TFAP2A mRNA stability Minghua Liao1,2†, Chunyu Li1,2†, Rui Yang3, Jun Li1, Ke Wu1,2, Jiayi Zhang1,2, Qian Zhu1,2, Yingchang Shi1,2 and Xianming Zhang1* Abstract Background HNRNPC is an RNA-binding protein that is overexpressed in a variety of cancers and is well known as an m6A “reader”, but its specific function and molecular mechanism in NSCLC have not been fully understood. This study aimed to discuss molecular mechanism of HNRNPC in NSCLC. Methods HNRNPC expression and clinically relevant data in pan-cancer and LUAD were extracted through these websites, including UALCAN, TIMER2 and GEPIA. The target gene of HNRNPC were identified through RIP-seq, meRIPqPCR and mRNA stability test. The differential expression of target gene in NSCLC was explored by immunohistochemistry. Lentivirus was selected to knock down HNRNPC and plasmid was selected to overexpress downstream target genes. The transfection efficiency was verified by RT-qPCR and Western Blot. In vitro colony formation assay, CCK-8, wound healing, transwell assays were performed to determine the biological functions of HNRNPC and target gene in lung adenocarcinoma cells. Results HNRNPC can promotes the expression ofTFAP2A by recognizing the m6A modification ofTFAP2A mRNA and maintaining its stability, activates the TFAP2A/CTNNB1 axis, enhances EMT, and ultimately promotes the malignant process of NSCLC and promote distant metastasis of NSCLC. Conclusions These results supported that HNRNPC regulate TFAP2A to promote the malignant progression and EMT of NSCLC. These findings connect m6A modification with EMT, providing a new perspective on the regulation of m6A modification in tumors. Keywords NSCLC, HNRNPC, TFAP2A, N6-methylation, Epithelial to mesenchymal transition †Minghua Liao and Chunyu Li equally contributed to the manuscript. *Correspondence: Xianming Zhang [zxm13078524367@163.com](zxm13078524367@163.com); [zhangxianming@gmc.edu.cn](zhangxianming@gmc.edu.cn) 1 Department of Respiratory and Critical Medicine, The Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, Guizhou 550004, China 2 School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, China 3 Department of Internal Medicine, Guiyang First People’s Hospital, Guiyang, Guizhou 550004, China Introduction Lung cancer is the leading cause of cancer-related death in the world [1]. The main pathological classifications are small cell lung cancer and non-small cell lung cancer (NSCLC), with NSCLC accounting for about 80–85% of cases [2]. NSCLC consists mainly of adenocarcinoma and squamous cell carcinoma, which account for more than 70% of the total risk of NSCLC [3]. And for patients with NSCLC with metastasis, treatment outcomes and prognosis remain poor [4]. Hence, further elucidation of NSCLC metastasis mechanisms and identification of © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory re

FAQs

What is HNRNPC and why is it studied in NSCLC?

HNRNPC is an m6A RNA-binding protein overexpressed in many cancers. Its specific function and molecular mechanism in NSCLC have not been fully understood, motivating this study.

How does HNRNPC influence TFAP2A in NSCLC?

HNRNPC increases TFAP2A expression by recognizing m6A modification on TFAP2A mRNA and maintaining its stability.

What cellular processes are affected by HNRNPC-mediated TFAP2A regulation?

The study reports activation of the TFAP2A/CTNNB1 axis, enhancement of EMT, promotion of malignant progression, and increased distant metastasis in NSCLC.

Sep 24, 2026

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