LncRNA H19 Activates the RAS-MAPK Signaling Pathway via miR-140-5p/SOS1 Axis in Malignant Liver Tumors
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View abstract on PubMed
Summary
This summary is machine-generated.Long non-coding RNA H19 (H19) promotes liver cancer progression by activating the Ras-MAPK pathway. This involves H19 interacting with miR-140-5p to upregulate SOS1, driving malignant liver tumor cell growth and invasion.
Area Of Science
- Oncology
- Molecular Biology
- Gene Regulation
Background
- Hepatocellular carcinoma (HCC) is a major global health concern with complex molecular underpinnings.
- Long non-coding RNAs (lncRNAs) are emerging as critical regulators in various cancers, including liver cancer.
- Understanding the role of specific lncRNAs like H19 is crucial for identifying novel therapeutic targets.
Purpose Of The Study
- To investigate the functional role of LncRNA H19 (H19) in malignant liver tumor cells.
- To elucidate the molecular mechanisms by which H19 influences liver cancer progression.
- To explore the potential interactions between H19, microRNAs, and signaling pathways in liver tumorigenesis.
Main Methods
- Quantitative RT-PCR to assess H19 expression in tumor and normal tissues/cells.
- Cell viability and Matrigel invasion assays to evaluate H19's impact on proliferation and metastasis.
- Luciferase reporter assays to confirm the interaction between miR-140-5p and SOS1.
- Western blot and pull-down assays to analyze the Ras-MAPK signaling pathway activation.
Main Results
- H19 expression was significantly lower in liver cancer tissues compared to normal tissues.
- H19 overexpression promoted proliferation and invasion in liver cancer cell lines (HepG2, SMMC-7721).
- H19 upregulated activated Ras and downstream components (p-Raf, p-ERK, p-MEK) of the Ras-MAPK pathway.
- H19 increased SOS1 protein levels, and miR-140-5p was identified as a direct targeting molecule of SOS1.
Conclusions
- LncRNA H19 plays a oncogenic role in malignant liver tumor cells.
- H19 activates the Ras-MAPK signaling pathway through the miR-140-5p/SOS1 axis.
- This pathway activation contributes to enhanced cell proliferation and invasion in liver cancer.
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