OVER KANSERİ HÜCRELERİNDE PRİMA-1 Met TEDAVİSİNE YANIT OLARAK DEĞİŞEN miRNA EKSPRESYON ANALİZİ

Yıl 2020, , 19 - 25, 04.05.2020

Nilüfer İmir , Esra Aydemir , Ece Şimşek

https://doi.org/10.34108/eujhs.543409

Öz

Tümör hücrelerinde p53
fonksiyonunun restorasyonu, over kanseri tedavisinde çekici bir strateji olacağı
düşünülmektedir, çünkü p53 mutasyonlarının over kanserlerinde görülme
sıklığı  %50-60 arasındadır. Küçük
molekül Prima-1^Met'in, p53'ün tümör baskılama fonksiyonunu geri
kazandığı ve insan tümör hücrelerinde hücre
büyümesini inhibe ettiği ve apoptozu indüklediği gösterilmiştir. MikroRNA'lar hem transkripsiyonel hem de translasyonel
seviyelerde gen ekspresyonunu düzenler ve hücre proliferasyonu, farklılaşma ve
hematopoez gibi çok çeşitli fizyolojik ve biyolojik süreçlerde etki yapar.
Epitelyal over kanserinde yapılan çok sayıdaki miRNA profillemesi
çalışmalarında, kemoterapi direnci ve hastalık progresyonu ile ilişkili
miRNA'lar tanımlanmıştır, fakat, Prima-1^Met'e yanıt olarak
miRNA'ların tutulumu hakkında çok az şey bilinmektedir. Bu çalışmada, apoptotik
etkisi olduğu bilinen Prima-1^Met ile
muamele edilmiş over kanseri hücre hatlarında, bu ilaca yanıt olarak
ekspresyonu değişen miRNA’ların belirlenmesini hedeflendi ve bunun için ilaç
verilen hücre hatlarında hem kanser hem de apoptosis yolaklarını hedefleyen
miRNA’ların ekspresyonları miScript PCR array ile belirlenip analiz edilmiştir.
Analiz sonucunda, her iki hücre hattında da hem over kanseri hem de
apoptosisle ilişkili olarak Prima-1^Metuygulamasıyla
ekspresyonu artan miRNA’lar; miRNA-1, miRNA-134, miRNA-141, miRNA-143,
miRNA-145, miRNA-204, miRNA-205, miRNA-214, miRNA-29a ve miRNA-29c olarak
belirlenmiştir. Ekspresyonu azalan miRNA’lar ise miRNA-21, miRNA-221 ve
miRNA-222 olarak tespit edilmiştir. Bu çalışma Prima-1^Met indüklü
apoptosisin moleküler mekanizmasının aydınlatılması için bir temel
oluşturmaktadır. 

Anahtar Kelimeler

Prima-1Met, miRNA, PCR-array, over kanseri, ekspresyon

ANALYSIS OF DIFFERENTIAL miRNA EXPRESSION IN RESPONSE TO PRIMA-1 Met THERAPY IN OVARIAN CANCER CELLS

Öz

Restoration of p53 function in tumor cells will be an attractive
strategy for ovarian cancer therapy since p53 mutations are found in more than
50 % of ovarian cancers. The small molecule Prima-1^Met has been
shown to restore tumor suppression function of p53, inhibit cell growth and
induce apoptosis in human tumor cells. MicroRNAs (miRNAs) regulate gene
expression at both transcriptional and translational levels as well as acting in
a wide variety of physiological and biological processes. Numerous miRNAs
associated with chemotherapy resistance and disease progression have been
described in a large number of miRNA profiling studies in epithelial ovarian
cancer, but little is known about the involvement of miRNAs in response to Prima-1^Met.
We aimed to determine the expression of miRNAs in response to Prima-1^Met
treatment, which is known to have apoptotic effects in ovarian cancer cell
lines. The expressions of miRNAs targeting both cancer and apoptosis pathways
in drug-delivered cell lines were determined and analyzed by miScript PCR
array. As a result of the assay, the expression of miRNA-1, miRNA-134,
miRNA-141, miRNA-143, miRNA-145, miRNA-204, miRNA-205, miRNA-214, miRNA-29a and
miRNA-29c increased in response to Prima-1^Met in both cell lines,
while the expression of miRNA-21, miRNA-221 and miRNA-222 was reduced. In
conclusion, this study provides a basis for elucidating the molecular mechanism
of Prima-1^Met-induced apoptosis.

Anahtar Kelimeler

Prima-1Met, miRNA, PCR-array, ovarian cancer, expression

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