Background
The hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA (HEIH) has been identified to act as an oncogene to promote cell tumorigenesis in hepatocellular carcinoma (HCC); however, the roles of HEIH in sorafenib resistance in HCC cells remain elusive.
Materials and Methods
The expression of HEIH and microRNA (miR)-98-5p was detected using quantitative real-time polymerase chain reaction. Cell viability, apoptosis, migration and invasion were analyzed using cell counting kit-8 assay, flow cytometry and transwell assay. Western blot was used to measure the levels of apoptosis-related protein and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein. The interaction between HEIH and miR-98-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay. In vivo experiments were performed using murine xenograft models.
Results
HEIH was up-regulated in sorafenib-resistant HCC tissues and cell lines, and HEIH silence weakened sorafenib resistance by suppressing cell viability, invasion and migration, decreasing the IC
50
values to sorafenib, and increasing apoptosis in sorafenib-resistant HCC cells in vitro and reinforced the anti-tumor effects of sorafenib in vivo. HEIH was a sponge of miR-98-5p, and miR-98-5p inhibition reversed the sorafenib sensitivity induced by HEIH deletion in sorafenib-resistant HCC cells. MiR-98-5p inhibition could activate PI3K/AKT pathway, and enhanced sorafenib resistance by regulating the activation of PI3K/AKT pathway in sorafenib-resistant HCC cells. Besides, HEIH also activated PI3K/AKT pathway through regulating miR-98-5p in sorafenib-resistant HCC cells.
Conclusion
HEIH conferred an advantage to sorafenib resistance in HCC by the activation of PI3K/AKT pathway through miR-98-5p, indicating a potential therapeutic strategy for HCC chemotherapy.
BackgroundTransposable elements (TEs) are common and often present with high copy numbers in cellular genomes. Unlike in cellular organisms, TEs were previously thought to be either rare or absent in viruses. Almost all reported TEs display only one or two copies per viral genome. In addition, the discovery of pandoraviruses with genomes up to 2.5-Mb emphasizes the need for biologists to rethink the fundamental nature of the relationship between viruses and cellular life.ResultsHerein, we performed the first comprehensive analysis of miniature inverted-repeat transposable elements (MITEs) in the 5170 viral genomes for which sequences are currently available. Four hundred and fifty one copies of ten miniature inverted-repeat transposable elements (MITEs) were found and each MITE had reached relatively large copy numbers (some up to 90) in viruses. Eight MITEs belonging to two DNA superfamilies (hobo/Activator/Tam3 and Chapaev–Mirage–CACTA) were for the first time identified in viruses, further expanding the organismal range of these two superfamilies. TEs may play important roles in shaping the evolution of pandoravirus genomes, which were here found to be very rich in MITEs. We also show that putative autonomous partners of seven MITEs are present in the genomes of viral hosts, suggesting that viruses may borrow the transpositional machinery of their cellular hosts’ autonomous elements to spread MITEs and colonize their own genomes. The presence of seven similar MITEs in viral hosts, suggesting horizontal transfers (HTs) as the major mechanism for MITEs propagation.ConclusionsOur discovery highlights that TEs contribute to shape genome evolution of pandoraviruses. We concluded that as for cellular organisms, TEs are part of the pandoraviruses’ diverse mobilome.Electronic supplementary materialThe online version of this article (10.1186/s13100-018-0125-4) contains supplementary material, which is available to authorized users.
Toona sinensis, whose young leaves and shoots are edible and nutritious, is a perennial deciduous tree vegetable. In this paper, the volatile constituents of dehydrated fresh young leaves of Toona sinensis obtained by different drying methods were micro-extracted in solid-phase, and then analyzed with gas chromatography-mass spectrometry (GC-MS). The major flavor components include caryophyllene, aromadendrene, nonadecane, and phytol. Comparing with convection oven drying and natural solar drying, vacuum drying and microwave drying can preserve most of the original flavors of Toona sinensis.
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