An article published this year in “CELL DEATH AND DISEASE” using our Annexin-V–Allophycocyanin (APC)/Propidium Iodide (PI)
double staining, by our customers from Humanitas Clinical and Research Center, Rozzano,
Italy, in the analysis of how MicroRNA-26a/cyclin-dependent kinase 5 axis
controls proliferation, apoptosis and in vivo tumor growth of diffuse large
B-cell lymphoma cell lines. Congrats and Thanks.
Summary:
Diffuse large B-cell lymphoma
(DLBCL) is the most frequent type of non-Hodgkin lymphoma. Despite a favorable
therapeutic response to first-line chemo-immunotherapy, still 30–40% of
patients is refractory, or relapse after this treatment. Thus, alternative
strategies must be sought. Previous studies have indicated that
cyclin-dependent kinase 5 (CDK5), a serine/threonine protein kinase, is
involved in tumor development and progression, and it may represent a potential
therapeutic target. However, its role in modulating DLBCL growth and
progression remains largely unexplored. In this study, we show that CDK5 and
its activator, cyclin-dependent kinase 5 activator 1 (CDK5R1 or p35), are
overexpressed in DLBCL cell lines and that signal transducer and activator of
transcription 3 (STAT3) phosphorylation and activity is dependent on CDK5
expression in DLBCL. Using public data sets, we also demonstrate that patients
with DLBCL show a higher expression of CDK5 compared with healthy individuals.
By using loss-of-function approaches, we demonstrate that CDK5’s activity
regulates proliferation and survival of DLBCL cells. MicroRNAs (miRNAs or miRs)
are small noncoding RNAs that negatively regulating gene expression and are
involved in cancer initiation and progression. We identify miR-26a as direct
regulator of p35 expression and CDK5 activity. We show that miR-26a expression
is lower in DLBCL cell lines compared to B lymphocytes and that its ectopic
expression leads to a drastic reduction of DLBCL tumor growth in vivo and decreased
proliferation, cell-cycle progression, and survival in vitro. Remarkably,
concomitant overexpression of a 3′-UTR-truncated form of p35 promoted tumor
growth in vivo and cell proliferation, cell-cycle progression, and cell
survival in vitro. In conclusion, these results demonstrate an important role
for miR-26a and CDK5 together in the survival and growth of DLBCL cells,
suggesting the existence of potential novel therapeutic targets for the
treatment of DLBCL.
Reference:
Product link:
Annexin-V–Allophycocyanin
(APC)/Propidium Iodide (PI) double staining: http://www.immunostep.com/57-annexin-v-anxv
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