Long noncoding RNA CASC11 promotes hepatocarcinogenesis and HCC progression through EIF4A3-mediated E2F1 activation

Area of Science:

• Oncology
• Molecular Biology
• RNA Biology

Background:

• Long noncoding RNAs play critical roles in cancer development.
• Cancer susceptibility candidate 11 (CASC11) is implicated in various cancers, including hepatocellular carcinoma (HCC).
• The precise role and underlying mechanisms of CASC11 in HCC require further elucidation.

Purpose of the Study:

• To investigate the role and mechanism of CASC11 in hepatocellular carcinoma (HCC) progression.
• To evaluate CASC11 as a potential diagnostic biomarker and therapeutic target for HCC.

Main Methods:

• Assessed CASC11 expression and prognostic value in HCC patients using RT-qPCR, western blotting, and in situ hybridization.
• Investigated CASC11's function in HCC tumorigenesis via proliferation, migration, glucose metabolism, apoptosis assays, and xenograft models.
• Explored molecular interactions between CASC11, E2F1, and EIF4A3 using molecular biology techniques including RIP and ChIP assays.

Main Results:

• CASC11 was upregulated in HCC tissues and correlated with poor prognosis.
• Inhibition of CASC11 suppressed HCC cell proliferation, migration, and glucose metabolism, while promoting apoptosis.
• CASC11 stabilizes E2F1 mRNA via EIF4A3 recruitment, impacting NF-κB and PI3K/AKT/mTOR pathways and PD-L1 expression. YY1 was identified as a regulator of CASC11 expression.

Conclusions:

• CASC11 promotes HCC progression through EIF4A3-mediated upregulation of E2F1.
• CASC11 represents a promising diagnostic biomarker and therapeutic target for HCC.