Dataset Information

MiR-942 decreases TRAIL-induced apoptosis through ISG12a downregulation and is regulated by AKT.

ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive death ligand in targeted cancer therapy. Many cancer cells are refractory to TRAIL-induced cell death and the mechanisms underlying resistance are unclear. The molecular mechanisms of HCC and gastric cancer cells resistant to TRAIL-induced apoptosis were explored using molecular biological and immunological methods. In vivo experiments were conducted to study the effect of interferon stimulated gene 12a (ISG12a) on human liver cancer xenografts in mice. ISG12a decreases in TRAIL-resistant cancer cells. ISG12a regulates the sensitivity of cancer cells to TRAIL in vitro and in vivo. MicroRNA-942 (miR-942) is inversely correlated with ISG12a expression in cancer cells and tissues. Forced expression of miR-942 in TRAIL-sensitive cells significantly reduces endogenous ISG12a level and changes the TRAIL sensitive phenotype to a resistant one. Knockdown of miR-942 expression in TRAIL-resistant cells restores the expression of ISG12a and sensitizes the cells to TRAIL treatment. AKT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Downregulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype of cancer cells and favors cancer cell survival. MiR-942 may offer a novel drug response marker with important implications in designing new therapeutics for TRAIL resistant tumors.

SUBMITTER: Liu N

PROVIDER: S-EPMC4148114 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

miR-942 decreases TRAIL-induced apoptosis through ISG12a downregulation and is regulated by AKT.

Liu Nianli N Zuo Chaohui C Wang Xiaohong X Chen Tianran T Yang Darong D Wang Jing J Zhu Haizhen H

Oncotarget 20140701 13

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive death ligand in targeted cancer therapy. Many cancer cells are refractory to TRAIL-induced cell death and the mechanisms underlying resistance are unclear. The molecular mechanisms of HCC and gastric cancer cells resistant to TRAIL-induced apoptosis were explored using molecular biological and immunological methods. In vivo experiments were conducted to study the effect of interferon stimulated gene 12a (ISG12a) on ...[more]

PMID: 24970806

Similar Datasets

Project description:Recent evidence has suggested that long non-coding RNAs (lncRNAs) may play a significant role in the pathogenesis of several neurological diseases, including spinal cord injury (SCI). However, little is known about the role of lncRNAs in SCI. The aim of the present study was to evaluate the potential functions of lncRNAs in SCI and to identify the underlying mechanisms of action. We firstly analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly-expressed lncRNAs which might be involved in the pathogenesis of SCI. The long non-coding RNA X-inactive specific transcript (XIST) was found to be one of the most significantly upregulated lncRNAs in the GEO dataset analysis, and is associated with apoptosis. We, therefore, selected this as a candidate lncRNA and investigated its function. We found that knockdown of lncRNA-XIST by Lv-shRNA had a prominent protective effect on SCI recovery by suppressing apoptosis through reactivation of the PI3K/AKT signaling pathway in rat spinal cord tissue. In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway. These results suggested that lncRNA-XIST knockdown may play an important role in limiting neuronal apoptosis in rats following SCI, and that the observed protective effects of lncRNA-XIST knockdown might have been mediated by its regulation on the phosphorylation of AKT by competitively binding miR-494. These findings have revealed, for the first time, the importance of the XIST/miR-494/PTEN/AKT signaling axis in the pathogenesis of SCI and suggest that lncRNA-XIST may be a promising molecular target for SCI therapy.

Dataset Information

MiR-942 decreases TRAIL-induced apoptosis through ISG12a downregulation and is regulated by AKT.

Publications

miR-942 decreases TRAIL-induced apoptosis through ISG12a downregulation and is regulated by AKT.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets