Lenvatinib-resistant hepatocellular carcinoma promotes malignant potential of tumor-associated macrophages via exosomal miR-301a-3p
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Lenvatinib-resistant hepatocellular carcinoma (LR HCC) promotes M2 macrophage polarization via exosomal miR-301a-3p. This crosstalk enhances cancer progression and lenvatinib resistance, offering a potential therapeutic target.
Area Of Science
- Oncology
- Cell Biology
- Molecular Medicine
Background
- MicroRNAs (miRNAs) mediate interactions between cancer cells and tumor-associated macrophages (TAMs), influencing malignancy and drug resistance.
- The specific mechanisms by which lenvatinib-resistant hepatocellular carcinoma (LR HCC) impacts TAM biology remain largely unexplored.
- Understanding this crosstalk is crucial for overcoming therapeutic resistance in HCC.
Purpose Of The Study
- To investigate the intercellular communication between LR HCC cells and TAMs mediated by exosomal miRNAs.
- To elucidate the role of specific miRNAs in promoting TAM polarization and enhancing HCC progression and lenvatinib resistance.
Main Methods
- Bioinformatic analysis identified miRNAs targeting PTEN.
- Exosomal miRNA expression was analyzed in LR HCC conditioned medium (CM).
- Macrophage phenotype and signaling pathways (PTEN-Nrf2) were assessed after co-culture with LR HCC CM, and HCC cells were subsequently cultured with modified TAMs.
Main Results
- LR HCC cells induced M2-like macrophage polarization more effectively than naïve HCC cells.
- Exosomal miR-301a-3p was upregulated in LR HCC CM, activating the PTEN/PI3K/GSK3β/Nrf2 pathway in TAMs.
- Exposure to conditioned LR TAMs increased HCC malignant potential and lenvatinib resistance; inhibiting exosomal miR-301a-3p reversed these effects.
Conclusions
- Exosomal miR-301a-3p derived from LR HCC cells drives M2 TAM polarization and activates Nrf2 signaling.
- This miRNA-mediated crosstalk contributes significantly to HCC progression and lenvatinib resistance.
- Exosomal miR-301a-3p represents a potential therapeutic target for overcoming lenvatinib resistance in HCC.
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
Related Concept Videos
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...