The Role of MEG3 in the Activation of Toll Like Receptor 3 in Prostate Cancer Cells

Year 2021, , 625 - 630, 22.09.2021

Merve Nur İnce , Asuman Deveci Özkan , Erhan Bezdegümeli , Ahmet Yasir Men , Bilge Nur Küçükakça , Gamze Güney Eskiler

https://doi.org/10.31832/smj.874417

Abstract

Objective: Prostate cancer accounts for approximately 10% of new cases diagnosed in men worldwide. Toll like receptors (TLRs) play a crucial role in the progression of cancer. Furthermore, the expression level of TLRs is mediated by different transcription factors and non-coding RNAs. Therefore, the aim of this study was to investigate the potential regulatory role of MEG3 and the interaction of TLR3 with MEG3 in the prostate cancer cells.
Materials and Methods: In this study, PC-3, LNCaP and HUVEC cells were used. To stimulate TLR3 expression, Poly I:C was used for a ligand of TLR3 and the less cytotoxic concentration of Poly I:C was determined by WST-1 analysis. The relative gene expression levels of TLR3 and MEG3 were analyzed by RT-PCR.
Results: According to the results, 5 µM of Poly I:C was chosen as a less cytotoxic concentration for the stimulation of TLR3 activity. The mRNA level of MEG3 (3.19-, 1.90-, and 1.90-fold) and TLR3 (6.17-, 5.75- and 2.27-fold) was significantly increased in PC-3, LNCaP and HUVEC cells, respectively after Poly I:C stimulation (p<0.05). Additionally, the expression level of MEG3 was 2.33- and 10.93-fold for PC-3 and LNCaP cells respectively, compared to HUVEC cells (p<0.05).
Conclusion: In conclusion, the activation of the TLR3 signaling pathway through Poly I:C promoted the level of MEG3 expression especially in castration-resistant prostate cancer cells. Thus, our preliminary data suggests that MEG3 could modulate TLR3 signaling pathway in prostate cancer cells.

Keywords

Prostate cancer, TLR3, MEG3, Poly I:C

Supporting Institution

Scientific and Technological Research Council of Turkey (TÜBİTAK)-2209-A-Research Project Support Programme for Undergraduate Students

Project Number

1919B011900829

Thanks

This work was supported by the Scientific and Technological Research Council of Turkey, [TUBITAK] under 2209-A-Research Project Support Programme for Undergraduate Students Grant [number 1919B011900829].

MEG3’ün Prostat Kanseri Hücrelerindeki Toll Benzeri Reseptör 3 Aktivasyonundaki Rolü

Abstract

Amaç: Dünya genelinde erkeklerdeki yeni kanser tanılarının yaklaşık %10'unu prostat kanseri oluşturmaktadır. Toll-benzeri reseptörler (TLR), prostat kanseri gelişiminde önemli rol oynamaktadır. Ayrıca TLR’lerin ekspresyon seviyesi çeşitli transkripsiyon faktörleri ve kodlanmayan RNA’lar ile düzenlenmektedir. Bu nedenle bu çalışmada MEG3’ün potansiyel düzenleyici rolünün ve TLR3-MEG3 ilişkisinin belirlenmesi amaçlanmaktadır.
Gereç ve Yöntemler: Bu çalışmada PC-3, LNCaP ve HUVEC hücreleri kullanılmıştır. Poli I:C; bir TLR3 ligandı olarak TLR3 ekspresyonunu uyarmak için kullanılmıştır. Poli I:C' nin toksik olmayan konsantrasyonu WST-1 analizi ile belirlenmiştir. TLR3 ve MEG3'ün relatif gen ekspresyon seviyeleri RT-PCR ile analiz edilmiştir.
Bulgular: Sonuçlara göre, 5 µM Poli I:C TLR3’ü aktive edilmesi için toksik olmayan konsantrasyon olarak seçilmiştir. MEG3 (3.19-, 1.90- ve 1.90-kat) ve TLR3 (6.17-, 5.75- ve 2.27-kat) mRNA seviyelerinin Poli I:C uygulamasından sonra sırasıyla PC-3, LNCaP ve HUVEC hücrelerinde anlamlı bir şekilde arttığı belirlenmiştir (p<0.05). Ayrıca, MEG3'ün mRNA seviyesi, HUVEC hücrelerine kıyasla PC-3 ve LNCaP hücrelerinde sırasıyla 2.33- ve 10.93- kat olarak tespit edilmiştir (p<0.05).
Sonuç: Sonuç olarak, Poli I:C aracılığıyla uyarılan TLR3 sinyal yolunun aktivitesi özellikle kastrasyon dirençli prostat kanseri hücrelerinde, MEG3 ekspresyon seviyesini arttırmıştır. Ön verilerimiz prostat kanserinde MEG3’ün TLR3 sinyal yolağını düzenleyebildiğini göstermektedir.

Keywords

Prostat kanseri, TLR3, MEG3, Poli I:C

Project Number

1919B011900829

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