MALAT1 modulated FOXP3 ubiquitination then affected GINS1 transcription and drived NSCLC proliferation

Area of Science:

• Oncology
• Molecular Biology
• Gene Regulation

Background:

• Long noncoding RNAs (lncRNAs) are implicated in cancer-associated protein post-translational modifications (PTMs).
• The precise regulatory roles of lncRNAs in non-small-cell lung carcinoma (NSCLC) proliferation, particularly concerning PTMs, remain largely unelucidated.
• Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and GINS complex subunit 1 (GINS1) are upregulated and promote NSCLC progression.

Purpose of the Study:

• To investigate the clinicopathologic significance of MALAT1 and GINS1 in NSCLC.
• To elucidate the regulatory mechanism of MALAT1 in NSCLC proliferation via PTMs.
• To identify the novel regulatory axis involving MALAT1, FOXP3, and GINS1 in NSCLC.

Main Methods:

• Analysis of the clinicopathologic significance and expression correlation between MALAT1 and GINS1 in NSCLC.
• In vitro and in vivo experiments involving MALAT1 silencing and GINS1 upregulation.
• Identification of FOXP3 as a transcription factor for GINS1 and investigation of MALAT1's interaction with FOXP3 and STUB1.

Main Results:

• A positive correlation was observed between MALAT1 and GINS1 expression in NSCLC.
• MALAT1 silencing inhibited NSCLC proliferation by decreasing GINS1 expression, while GINS1 upregulation reversed this inhibition.
• MALAT1 stabilizes FOXP3 by binding to its ZF and LZ domains, inhibiting STUB1-mediated ubiquitination and consequently affecting GINS1 transcription.

Conclusions:

• A novel regulatory axis, MALAT1-FOXP3-GINS1, was identified in NSCLC.
• MALAT1 plays a crucial role in modulating FOXP3 PTMs, influencing GINS1 transcription and driving NSCLC proliferation.
• Targeting the MALAT1-FOXP3-GINS1 axis presents a potential therapeutic strategy for NSCLC.