* The pan-deacetylase inhibitor panobinostat suppresses the expression of oncogenic miRNAs in hepatocellular carcinoma cell lines.
- Deacetylase inhibitors (DACi) are a new class of drugs with a broad spectrum of mechanisms that favor their application in cancer therapy. Currently, the exact mechanisms and cellular effects of DACi have not been fully elucidated. In addition to their effects on histone acetylation, DACi can interfere with gene expression via miRNA pathways. Treatment with panobinostat (LBH589), a novel potent DACi, led to the highly aberrant modulation of several miRNAs in hepatocellular carcinoma (HCC) cell lines as shown by miRNA array analysis. Among them, hsa-miR-19a, hsa-miR-19b1 and the corresponding precursors were down-regulated by panobinostat in TP53(-/-) Hep3B and TP53(+/+) HepG2 cell lines; hsa-miR30a-5p mature form only was suppressed in both HCC cell lines, as confirmed by further RT-qPCR analysis. In HCC cell lines, panobinostat caused the upregulation of the predicted miRNA targets APAF1 and Beclin1 protein levels. Transfection with oligonucleotides mimicking these miRNAs led to an increase in the viability rate of both cell lines as analyzed by impedance-based real-time cell analysis. In addition, transfecting miRNA mimicking oligonucleotides resulted in the decrease of APAF1, Beclin1 and PAK6 at the protein level, proving the regulating influence of the investigated miRNAs on gene final products. The overexpression of the above mentioned oncomiRs in Hep3B and HepG2 cell lines leads to cell proliferation and downregulation of cell death associated proteins. In our model, panobinostat exerts its anti-cancer effect by suppressing these miRNAs and restoring the expression of their corresponding tumor suppressor targets.
=>新発見の, 新しい, 現代的な, 新参の
Overview of adj new
The adj new has 11 senses (first 5 from tagged texts)
1. (310) new -- (not of long duration; having just (or relatively recently) come into being or been
made or acquired or discovered; "a new law"; "new cars"; "a new comet"; "a new friend"; "a new
year"; "the New World")
2. (36) fresh, new, novel -- (original and of a kind not seen before; "the computer produced a
completely novel proof of a well-known theorem")
3. (11) raw, new -- (lacking training or experience; "the new men were eager to fight"; "raw
recruits")
4. (5) new, unexampled -- (having no previous example or precedent or parallel; "a time of
unexampled prosperity")
5. (3) new -- (other than the former one(s); different; "they now have a new leaders"; "my new car
is four years old but has only 15,000 miles on it"; "ready to take a new direction")
6. new -- (unaffected by use or exposure; "it looks like new")
7. newfangled, new -- ((of a new kind or fashion) gratuitously new; "newfangled ideas"; "she buys
all these new-fangled machines and never uses them")
8. New -- (in use after medieval times; "New Eqyptian was the language of the 18th to 21st
dynasties")
9. Modern, New -- (used of a living language; being the current stage in its development; "Modern
English"; "New Hebrew is Israeli Hebrew")
10. new, young -- ((of crops) harvested at an early stage of development; before complete maturity;
"new potatoes"; "young corn")
11. new -- (unfamiliar; "new experiences"; "experiences new to him"; "errors of someone new to the
job")
Overview of adv new
The adv new has 1 sense (first 1 from tagged texts)
1. (1) newly, freshly, fresh, new -- (very recently; "they are newly married"; "newly raised
objections"; "a newly arranged hairdo"; "grass new washed by the rain"; "a freshly cleaned floor";
"we are fresh out of tomatoes")
--- WordNet end ---