Scholarlink

Background <p>Alternative splicing contributes to the carcinogenic process of non-small cell lung cancer. Although extensive efforts have characterized cancer-associated alternative splicing events, the upstream regulators governing these aberrant splicing events remain poorly understood.</p> Methods <p>Here, we integrated multi-omics data from 22 lung adenocarcinoma, 13 lung squamous cell carcinoma and matched adjacent normal tissues of Chinese patients. We aimed to identify cancer-associated splicing events, construct regulatory networks of RBP, miRNA and DNA methylation on them and dissect carcinogenic pathways at integrated multi-omics layers in lung adenocarcinoma and squamous cell carcinoma, respectively.</p> Results <p>We identified that immune-suppression pathways and oxidative phosphorylation specifically promote the progression of adenocarcinoma and squamous cell carcinoma, respectively. <i>ATP5F1C</i> exon 9 inclusion in adenocarcinoma and <i>LTBP3</i> exon 25 exclusion in squamous cell carcinoma, involved in proliferation, invasion and metastasis, are key splicing events with therapeutic potential. Furthermore, we proposed <i>miR-4521</i>-<i>PABPC5</i>-<i>ATP5F1C</i>, <i>miR</i>-<i>4423</i>-<i>3p</i>-<i>IGF2BP3</i>/<i>miR</i>-<i>944</i>-<i>RBMS3</i>-<i>LTBP3</i> as upstream regulatory axes potentially driving these events. Notably, genome-wide CpG methylation exhibited widespread association with distant splicing events, potentially playing a trans-regulatory role by disrupting splice factor (<i>BCL11B</i>, <i>RUNX1</i>, <i>RUNX2</i>) binding near CpG sites and inhibiting <i>RBMS3</i> transcription.</p> Conclusions <p>Our findings shed light on the potential functional impact and multi-layer regulation of cancer-associated splicing events, offering novel insights for splicing-switching therapies to improve non-small cell lung cancer treatment and prognosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The identification of RNA splicing aberrations and their potential regulatory network in Chinese non-small cell lung cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月2日

查看全文
  • Yu Yan,
  • Hua Meng,
  • Huan Guo,
  • Sheng Wei,
  • Shanshan Cheng

摘要

Background

Alternative splicing contributes to the carcinogenic process of non-small cell lung cancer. Although extensive efforts have characterized cancer-associated alternative splicing events, the upstream regulators governing these aberrant splicing events remain poorly understood.

Methods

Here, we integrated multi-omics data from 22 lung adenocarcinoma, 13 lung squamous cell carcinoma and matched adjacent normal tissues of Chinese patients. We aimed to identify cancer-associated splicing events, construct regulatory networks of RBP, miRNA and DNA methylation on them and dissect carcinogenic pathways at integrated multi-omics layers in lung adenocarcinoma and squamous cell carcinoma, respectively.

Results

We identified that immune-suppression pathways and oxidative phosphorylation specifically promote the progression of adenocarcinoma and squamous cell carcinoma, respectively. ATP5F1C exon 9 inclusion in adenocarcinoma and LTBP3 exon 25 exclusion in squamous cell carcinoma, involved in proliferation, invasion and metastasis, are key splicing events with therapeutic potential. Furthermore, we proposed miR-4521-PABPC5-ATP5F1C, miR-4423-3p-IGF2BP3/miR-944-RBMS3-LTBP3 as upstream regulatory axes potentially driving these events. Notably, genome-wide CpG methylation exhibited widespread association with distant splicing events, potentially playing a trans-regulatory role by disrupting splice factor (BCL11B, RUNX1, RUNX2) binding near CpG sites and inhibiting RBMS3 transcription.

Conclusions

Our findings shed light on the potential functional impact and multi-layer regulation of cancer-associated splicing events, offering novel insights for splicing-switching therapies to improve non-small cell lung cancer treatment and prognosis.