Project description:The microRNA miR-146a regulates several aspects of chronic inflammation, including the Hepatocellular Carcinoma (HCC) risk factor hepatosteatosis. Here, we find that loss of miR-146a leads to significantly increased tumor burden in a mouse model of HCC. Notably, this miR-146a-/- phenotype is most pronounced in females, who are typically not sensitive to this model. Mechanistically, we identified increases in dysfunctional CD8+ T-cells that express high levels of CCL5 and resemble Taa cells, as well as elevated levels of myeloid cells that resemble monocytic myeloid-derived suppressor cells (M-MDSCs), a class of myeloid cells that suppress tumor immunity. Deletion of Ccl5 from miR-146a-deficient mice returned tumor growth and the aberrant myeloid cell population to wild-type (WT) levels. Surprisingly, deletion of Ccl5 did not rescue the gross metabolic phenotype observed in miR-146a-/- mice subjected to HCC induction, indicating independent roles for miR-146a in its regulation of HCC and metabolic disease. Taken together, this work reveals a critical host protective role for miR-146a in HCC through suppression of CCL5, providing an impetus for targeting these pathways as a means to combat HCC. Further, the correlations with disease and Taa cells suggest that aging may increase HCC risk through the accumulation of Taa cells.
Project description:p53 suppresses tumor progression and metastasis by regulating a large set of genes and microRNAs. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 upregulates microRNAs including miR-200 and miR-192 family members.
Project description:Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to limited diagnostic and therapeutic options. Non-coding RNAs, such as microRNAs (miRNAs), play key roles in cancer biology. Our previous findings showed that miR-423-5p exerts anti-cancer effects on HCC patients treated with sorafenib by promoting autophagy. In this study, we investigated the molecular mechanisms underlying its activity by generating SNU-387 HCC cell line stably overexpressing miR-423-5p and conducting a comprehensive proteomic analysis. Mass spectrometry profiling identified 698 differentially expressed proteins (DEPs) in miR-423-5p-overexpressing cells compared to controls. Functional enrichment analysis revealed significant alterations in metabolic pathways, particularly purine/pyrimidine metabolism and gluconeogenesis. To relate these findings to clinical context, we integrated experimentally validated and predicted miR-423-5p targets with The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma (LIHC) dataset. Seven candidate proteins were significantly associated with patient prognosis (log-rank p < 0.05 for both overall and disease-free survival). These targets were downregulated in our miR-423-5p model but found to be upregulated in stage III HCC tissues from TCGA data.
2025-09-29 | PXD064869 | Pride
Project description:HERV2365 upregulates FGF1 expression by sponging miR326 to promote the progression of intrahepatic cholangiocarcinoma
Project description:mRNA expression profile modified by stable transfection of microRNA mir-517a (MIR517A) in a human hepatocellular carcinoma cell line Huh-7 Keywords: Hepatocellular carcinoma, Expression array, microRNA
Project description:mRNA expression profile modified by stable transfection of microRNA mir-517a (MIR517A) in a human hepatocellular carcinoma cell line Huh-7 Keywords: Hepatocellular carcinoma, Expression array, microRNA microRNA mir-517a (MIR517A) was transfected to Huh-7 cells using GFP-expressing lentiviral vector. Infected cells were selected using flow cytometry and subjected to mRNA expression microarray experiment. The profiles were compared to controls cells infected with only GFP protein.
