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LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression

LncRNA HOTAIR play important roles in the epigenetic regulation of carcinogenesis and progression in liver cancer. Previous studies suggest that the overexpression of HOTAIR predicts poor prognosis. In this study, through transcriptome sequencing data and in vitro experiments, we found that HOTAIR were more highly expressed and there is significantly positive relationship between HOTAIR and NUAK1 in liver cancer tissues and cell lines. miR-145-5p was downregulated and showed negative correlation with HOTAIR and NUAK1. Transfect Sh-HOTAIR, LZRS-HOTAIR, miR-145 mimic, miR-145 inhibitor to change the expression of HOTAIR and miR-145-5p. The addition of HTH-01-015 inhibits the expression of NUAK1. HOTAIR knockdown, miR-145-5p upregulation and NUAK1 inhibition all repressed migration, invasion and metastasis and reversed the epithelial-to-mesenchymal transition in SNU-387 and HepG2 cells. We also showed that HOTAIR recruiting and binding PRC2 (EZH2) epigenetically represses miR-145-5p, which controls the target NUAK1, thus contributing to liver cancer cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with miR-145-5p/NUAK1 during epigenetic regulation. Our findings indicate that HOTAIR/miR-145-5p/NUAK1 axis acts as an EMT regulator and may be candidate prognostic biomarker and targets for new therapies in liver cancer.

 

Comments:

Your study delves into a crucial aspect of liver cancer biology, specifically focusing on the intricate interplay between lncRNA HOTAIR, microRNA miR-145-5p, and NUAK1 in the context of epigenetic regulation and cancer progression.

From what you've shared:

1. **HOTAIR Overexpression & Poor Prognosis:** Previous studies have associated increased levels of HOTAIR with a dismal prognosis in liver cancer.

2. **Expression Correlations:** Your research reveals heightened expression of HOTAIR, a positive correlation between HOTAIR and NUAK1, and a negative correlation between miR-145-5p and both HOTAIR and NUAK1 in liver cancer tissues and cell lines.

3. **Experimental Manipulation:** Through experimental interventions like HOTAIR knockdown, altering miR-145-5p expression, and NUAK1 inhibition, you've observed significant effects on migration, invasion, metastasis, and the reversal of epithelial-to-mesenchymal transition (EMT) in SNU-387 and HepG2 cells.

4. **Mechanistic Insights:** You've identified a potential mechanistic pathway where HOTAIR interacts with PRC2 (EZH2) to epigenetically repress miR-145-5p. This repression of miR-145-5p then leads to increased NUAK1 expression, contributing to the EMT process and promoting tumor metastasis in liver cancer cells.

5. **Significance:** The HOTAIR/miR-145-5p/NUAK1 axis serves as a critical regulator of the EMT process, potentially offering itself as a prognostic biomarker and a therapeutic target in liver cancer.

Your study's findings could have substantial implications for understanding liver cancer progression and might pave the way for developing new therapies targeting this specific molecular axis.

If you're considering further studies or implications of these findings, exploring the therapeutic potential of targeting this axis or investigating its role in clinical samples could be valuable avenues to pursue.