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

IF 5.3 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-03-08 DOI:10.1186/s12935-025-03660-x

Minghua Liao, Chunyu Li, Rui Yang, Jun Li, Ke Wu, Jiayi Zhang, Qian Zhu, Yingchang Shi, Xianming Zhang

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引用次数: 0

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, meRIP-qPCR 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 of TFAP2A by recognizing the m6A modification of TFAP2A 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.

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HNRNPC通过维持TFAP2A mRNA的稳定性促进非小细胞肺癌的进展。

背景：HNRNPC是一种在多种癌症中过表达的rna结合蛋白，是众所周知的m6A“阅读器”，但其在NSCLC中的具体功能和分子机制尚不完全清楚。本研究旨在探讨HNRNPC在NSCLC中的分子机制。方法：通过UALCAN、TIMER2、GEPIA等网站提取HNRNPC在泛癌和LUAD中的表达及临床相关数据。通过RIP-seq、meRIP-qPCR和mRNA稳定性试验鉴定HNRNPC靶基因。应用免疫组织化学方法探讨靶基因在非小细胞肺癌中的差异表达。选择慢病毒敲低HNRNPC，选择质粒过表达下游靶基因。RT-qPCR和Western Blot验证转染效率。通过体外集落形成实验、CCK-8、伤口愈合、transwell实验，确定HNRNPC及其靶基因在肺腺癌细胞中的生物学功能。结果：HNRNPC可以通过识别TFAP2A mRNA的m6A修饰并维持其稳定性来促进TFAP2A的表达，激活TFAP2A/CTNNB1轴，增强EMT，最终促进NSCLC的恶性过程，促进NSCLC的远处转移。结论：这些结果支持HNRNPC调控TFAP2A促进NSCLC的恶性进展和EMT。这些发现将m6A修饰与EMT联系起来，为肿瘤中m6A修饰的调控提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.