Project description:Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma [mRNA, lncRNA]
Project description:To identify the novel tumor suppressors in hepatocellular carcinoma (HCC), we have employed whole genome microarray expression profiling as a discovery platform in HCC and paired normal liver tissues to identify genes which down-regulated in HCC. Among which, INTS6 and its pseudogene, namely INTS6P1, were found to be dramatically down-regulated in HCC. The down-regulated expression of INTS6 and INTS6P1 in HCC was further confirmed by real-time PCR. RNA was extracted from 3 pairs of HCC and normal liver tissue harvested from patients to undergo microarray study.
Project description:To identify the novel tumor suppressors in hepatocellular carcinoma (HCC), we have employed whole genome microarray expression profiling as a discovery platform in HCC and paired normal liver tissues to identify genes which down-regulated in HCC. Among which, INTS6 and its pseudogene, namely INTS6P1, were found to be dramatically down-regulated in HCC. The down-regulated expression of INTS6 and INTS6P1 in HCC was further confirmed by real-time PCR. RNA was extracted from 3 pairs of HCC and normal liver tissue harvested from patients to undergo microarray study.
Project description:To identify the novel tumor suppressors in hepatocellular carcinoma (HCC), we have employed whole genome microarray expression profiling as a discovery platform in HCC and paired normal liver tissues to identify genes which down-regulated in HCC. Among which, INTS6 and its pseudogene, namely INTS6P1, were found to be dramatically down-regulated in HCC. The down-regulated expression of INTS6 and INTS6P1 in HCC was further confirmed by real-time PCR.
Project description:To identify the novel tumor suppressors in hepatocellular carcinoma (HCC), we have employed whole genome microarray expression profiling as a discovery platform in HCC and paired normal liver tissues to identify genes which down-regulated in HCC. Among which, INTS6 and its pseudogene, namely INTS6P1, were found to be dramatically down-regulated in HCC. The down-regulated expression of INTS6 and INTS6P1 in HCC was further confirmed by real-time PCR.
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.
Project description:Post-transcriptional regulation of gene expression by miRNAs likely makes significant contributions to mRNA abundance at the embryo-maternal interface. In this study, we investigated how miR-26a-5p and miR-125b-5p contribute to molecular changes occurring in the uterine luminal epithelium, which serves as the first site of signal exchange between the mother and developing embryo. To measure de novo protein synthesis after miRNA delivery to primary uterine luminal epithelial cells, we employed pulsed stable isotope labeling by amino acids (pSILAC). We found that both miRNAs alter the proteome of luminal epithelial cells, impacting numerous cellular functions, immune responses, as well as intracellular and second messenger signaling pathways. Additionally, we identified several features of miRNA-mRNA interactions that may influence the targeting efficiency of miR-26a-5p and miR-125b-5p. Overall, our study suggests a complex interaction of miR-26a-5p and miR-125b-5p with their respective targets. However, both appear to cooperatively function in modulating the cellular environment of the luminal epithelium, facilitating the morphological and molecular changes that occur during the intensive communication between the embryo and uterus at pregnancy.
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:We report the application of miRNAs analysis in exosomes based on second-generation high-throughput sequencing. Plasma samples from 3 hepatocellular carcinoma patients and 3 healthy controls were collected, and exosomes were isolated by ultra-centrifugation. MiRNAs in exosomes were then extracted and high-throughput sequencing was performed.By comparing the sequencing data, we screened out differentially expressed miRNAs and validated them with qRT-PCR in exosome samples, establishing and verifying the diagnostic panel of hepatocellular carcinoma composed of miR-212-5p, miR-519b-3p, miR-1248 and miR-1250-5p.
