Project description:As miR-885-5p is a microRNA downregulated in Cutaneous Lupus Erythematosus (CLE) and it is localted in the epidemis and its function is focused in keratinocytes, human Arrays to study the role of miR-885-5p in Cutaneous Lupus Erythematosius will be conducted.Gene expression in keratinocytes transfected with anti-miR-885-5p will be studied. We have included 24 Samples: Non-stimulated control (4), Non-stimulated anti-miR-885-5p (4), UVB-stimulated control (4), UVB-stimulated antimiR-885-5p (4), IFN alpha-stimulated control (4) and IFN alpha-stimulated anti-miR-885-5p
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting messenger RNA (mRNA) for translational repression or degradation. Dysregulation of miRNAs has been implicated in hepatocellular carcinoma (HCC) development. Here, we identify miR-885-5p as a novel tumor suppressor miRNA in HCC. Analysis of miRNA expression profiles from TCGA and GEO databases revealed downregulation of miR-885-5p in HCC tissues. Overexpression of miR-885-5p significantly suppressed HCC cell proliferation, supporting its tumor-suppressive role. Transcriptomic profiling of miR-885-5p-overexpressing HCC cells identified cell cycle as the most affected pathway by KEGG and GO analyses. Specifically, miR-885-5p induced downregulation of G1/S transition-promoting genes, including CDK6, E2F2, and CCNA2, in HCC cells. Consequently, these cells exhibited reduced BrdU incorporation and G1 phase arrest. Dual luciferase assays confirmed direct interaction of miR-885-5p with the 3' untranslated regions of CDK6, E2F2, and CCNA2 mRNAs. Furthermore, miR-885-5p overexpression sensitized HCC cells to the CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib. These findings demonstrate that miR-885-5p induces cell cycle arrest and enhances CDK4/6 inhibitor sensitivity in HCC, suggesting its potential as a therapeutic target.
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, necessitating innovative therapeutic approaches. This study demonstrates that the compound CC-885 exerts potent anti-tumor effects in HCC both in vitro and in vivo. CC-885 significantly inhibited proliferation, migration, and invasion of HCC cells. In vivo, CC-885 markedly reduced tumor growth and angiogenesis in chick embryo and mouse xenograft models. Mechanistically, CC-885 selectively reduced GOLM1 protein levels via ubiquitin-mediated proteasomal degradation, without affecting its mRNA levels. GOLM1 knockdown mimicked the anti-proliferative effects of CC-885, while overexpression of GOLM1 conferred resistance to CC-885-induced apoptosis and growth inhibition. CC-885 facilitated the interaction between GOLM1 and the E3 ubiquitin ligase CRBN, promoting GOLM1 ubiquitination and degradation. Transcriptomic analyses revealed that CC-885 and GOLM1 knockdown modulated key pathways involved in apoptosis, NF-κB signaling, and cell proliferation. These findings highlight CC-885 as a promising therapeutic agent for HCC, primarily by facilitating the CRBN-dependent degradation of GOLM1, underscoring its potential for clinical application.