Regulatory role of lncH19 in RAC1 alternative splicing: implication for RAC1B expression in colorectal cancer.

Area of Science:

• Molecular Biology
• Cancer Biology
• RNA Biology

Background:

• Aberrant alternative splicing is crucial in cancer, influencing invasion, metastasis, and drug resistance.
• Colorectal cancer exhibits significant transcriptomic variations due to alternative splicing.
• Long non-coding RNAs (lncRNAs) regulate splicing by interacting with splicing factors and target genes.

Purpose of the Study:

• To investigate the role of long non-coding RNA H19 (lncH19) in colorectal cancer progression.
• To elucidate the mechanism by which lncH19 influences alternative splicing of target genes.
• To determine the relationship between lncH19, RAC1B, c-Myc, and Cyclin-D in colorectal cancer.

Main Methods:

• Bioinformatic analysis to identify lncH19-associated transcripts and splicing factor binding sites.
• In vitro experiments to confirm binding of splicing factors (hnRNPM, RBFOX2) to RAC1 and lncH19.
• Loss and gain of expression studies in colorectal cancer cell lines (SW620, HCT116).
• In vivo analysis of patient tumor biopsies.

Main Results:

• lncH19 binds to splicing factors hnRNPM and RBFOX2, and to RAC1 mRNA.
• lncH19 is essential for RAC1B expression, leading to increased c-Myc and Cyclin-D.
• Elevated levels of lncH19, RAC1B, c-Myc, and Cyclin-D were observed in colorectal cancer tissues compared to healthy tissues.
• A positive correlation was found between lncH19 and RAC1B expression in patients.

Conclusions:

• lncH19 acts as an oncogene in colorectal cancer by modulating alternative splicing.
• lncH19 facilitates the binding of RBFOX2 and hnRNPM to RAC1, promoting RAC1B expression.
• This mechanism contributes to colorectal cancer development and progression via RAC1B, c-Myc, and Cyclin-D upregulation.