Deep sequencing reveals a global reprogramming of lncRNA transcriptome during EMT

Area of Science:

• Molecular Biology
• Genomics
• Cancer Research

Background:

• Long non-coding RNAs (lncRNAs) are implicated in Epithelial-Mesenchymal Transition (EMT), a critical process in tumor metastasis.
• Global alterations in the lncRNA transcriptome during EMT remain largely uncharacterized.

Purpose of the Study:

• To investigate global lncRNA transcriptome changes during TGF-β-induced EMT.
• To identify key lncRNA regulators and novel lncRNA clusters involved in EMT progression.

Main Methods:

• Deep-sequencing of the whole transcriptome in MCF10A cells undergoing TGF-β-induced EMT.
• Co-expression network construction to identify lncRNA regulators.
• Analysis of lncRNAs located in gene desert regions.

Main Results:

• Global lncRNA transcriptome reprogramming was observed as early as 8 hours after TGF-β treatment.
• Expression of 3403 known and novel lncRNAs and 570 known and novel circRNAs were altered.
• A key lncRNA regulator, RP6-65G23.5, was identified, along with 216 lncRNA clusters in gene deserts exhibiting concurrent expression changes during EMT.

Conclusions:

• EMT involves a significant global reprogramming of the lncRNA transcriptome.
• Specific lncRNAs, including RP6-65G23.5 and clusters in gene deserts, play crucial roles in regulating EMT.
• These findings provide novel insights into the molecular mechanisms of EMT and potential targets for cancer therapy.