Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multidrug resistant genes are highly expressed in hepatocellular carcinoma that seriousty affects the effect of chemotherapy. Screening of resistant genes from HCC cells and studying its mechanism of drug resistance will be helpful to improve the effecacy of chemotherapy for hepatocellular carcinoma. Here we described an alternative method called cyclical packaging rescue (CPR). First we constructed a retrovirus cDNA library of hepatoma cells and used it to infect fibroblasts. Then we added drugs to screen survival cells. The survival cells, stably integrated helper-free retroviral libraries, were recovered rapidly after transfection with plasmids expressing retroviral gag-pol and env genes. Through this method, retroviral RNAs were directly repackaged into new infectious virions. Recovered retroviral supernatant was then used to reinfect fresh target cells. When performed in concert with selection using functional assays, cDNAs regulating functional responses could be identified by enrichment through multiple rounds of retroviral library recovery and retransmission. Using CPR, we obtained several cDNAs. After a preliminary detection, we found Ribosomal protein S11 (RPS11), Ribosomal protein L6 (RPL6), Ribosomal protein L11 (RPL11), Ribosomal protein L24 (RPL24) possibly had drug resistant function.
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PMID:[Screening of drug resistent gene by cyclical packaging rescue of hepatocellular carcinoma retroviral cDNA libraries]. 2738 70

LncRNAs have been associated with infection and hepatitis B virus (HBV)-related diseases, though the underlying mechanisms remain unclear. We obtained HBV-HCC lncRNA profiles by deep sequencing and found HOTTIP to be significantly upregulated. RT-qPCR indicated that HOTTIP is highly expressed in HBV-positive hepatoma tissue and induced by HBV in vitro. Virological experiments showed that HOTTIP significantly suppresses the generation of hepatitis B viral surface antigen (HBsAg), hepatitis B viral e antigen (HBeAg) and HBV replication. HOXA13, a downstream factor of HOTTIP, was found to bind to HBV Enh I/Xp to repress the production of HBV pregenome RNA (pgRNA) and total RNA as well as HBV replication, suggesting that HOXA13 mediates HOTTIP-induced suppression of HBV replication. More interestingly, HBV DNA pol binds to and stabilizes CREB1 mRNA to facilitate translation of the protein, which in turn binds to the regulatory element of HOTTIP to promote its expression. CONCLUSION: Our findings demonstrate that HBV DNA pol attenuates HBV replication via activation of the CREB1-HOTTIP-HOXA13 axis. These findings shed light on the mechanism by which HBV restrains replication to contribute to persistent infection.
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PMID:HBV DNA polymerase restrains viral replication via the CREB1-HOTTIP-HOXA13 axis. 3231 10