Coordinated effects of microRNA-494 induce G 2/M arrest in human cholangiocarcinoma.
Summary of "Coordinated effects of microRNA-494 induce G 2/M arrest in human cholangiocarcinoma."
MicroRNA (miRs) have emerged as salient regulators in cancer homeostasis and, recently, as putative therapeutics. Cholangiocarcinomas (CCA) are aggressive cancers with survival usually measured in months. mRNA arrays followed by pathway analysis revealed that miR-494 is a major modulator of the cell cycle progression from gap 2 (G 2) to mitosis (M). We performed fluorescence activated cell sorting (FACS) as well as differential interference contrast (DIC) microscopy, and confirmed that miR-494 induces a significant arrest in G 2/M in CCA cells. Furthermore, we verified that miR-494 modulates the protein level of six genes involved in the G 2/M transition: Polo-like Kinase 1 (PLK1), pituitary tumor-transforming gene 1 (PTTG1), Cyclin B1 (CCNB1), cell-division cycle 2 (CDC2), cell-division cycle 20 (CDC20) and topoisomerase II α (TOP2A). Next, we identified direct binding of miR-494 to the open reading frame (ORF) and downregulation of PTTG1 and TOP2A. In summary, our findings suggest that miR-494 has a global regulatory role in cell cycle progression, exerted by concerted effects on multiple proteins involved in gap 1 (G 1) to synthesis (S), as described previously, as well as G 2 to M progression. Therefore, it appears that the simultaneous effects of a single miR species on multiple targets along the same canonical pathway is advantageous for the usage of miRs as therapeutics. In addition, our data suggest that miRs act within a narrow range. miR expression above the upper threshold does not appear to induce further effects, which is reassuring in terms of off-target effects of miR surrounding noncancerous tissue.
Division of Gastroenterology and Hepatology; Johns Hopkins Hospital; Baltimore, MD USA.
This article was published in the following journal.
Name: Cell cycle (Georgetown, Tex.)
Medical and Biotech [MESH] Definitions
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
Physical manipulation of animals and humans to induce a behavioral or other psychological reaction. In experimental psychology, the animal is handled to induce a stress situation or to study the effects of "gentling" or "mothering".
Human Genome Project
A coordinated effort of researchers to map (CHROMOSOME MAPPING) and sequence (SEQUENCE ANALYSIS, DNA) the human GENOME.
Sinus Arrest, Cardiac
The omission of atrial activation that is caused by transient cessation of impulse generation at the SINOATRIAL NODE. It is characterized by a prolonged pause without P wave in an ELECTROCARDIOGRAM. Sinus arrest has been associated with sleep apnea (REM SLEEP-RELATED SINUS ARREST).
Out-of-hospital Cardiac Arrest
Occurrence of heart arrest in an individual when there is no immediate access to medical personnel or equipment.
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