In Silico Identification of miRNAs and Their Potential Target Genes Targeting SARS-CoV-2 RNA in the Male Reproductive System

Abstract

Aim: SARS-CoV-2 infection, which causes millions of deaths and morbidities worldwide, has caused many different pathologies at the molecular level in humans. Studies have shown that this virus can affect male reproductive cells. This study aimed to investigate in silico how SARS-CoV-2 infection may cause infertility through miRNAs. Material and Methods: The most expressed miRNAs in healthy testicular tissue were obtained from Tissue Atlas. Among these miRNAs, miRNAs determined to target COVID-19 RNA were listed in the miRDB database. The resulting list was compared with the miRWalk database which uses the machine learning algorithm. Common targets were matched using miRTarBase, a database of experimentally validated miRNA-target interactions, and subsequently TargetScan. Results: Testicular tissue-specific miRNAs that target the COVID-19 RNA sequence and whose endogenous levels were found to be affected in silico were identified. Of these, hsa-miR-195-5p, hsa-miR-16-5p, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-497-5p and hsa-miR-424-5p were determined to be members of the mir-15/16 family, and hsa-miR-30c-5p, hsa-miR-30b-5p, hsa-miR-30a-5p were revealed to be members of the mir-30 family. It was also shown that the potential target genes of these miRNAs include ABL2, BCL2, PLEKHA1, WNK3, CCNT2, DICER1, CCND1, CCND2, CCND3 and WEE1, which are related to cell cycle, DNA damage, apoptosis, spermatogenesis and viral response. Conclusion: This study shows that the expression of testicular tissue-specific miRNAs and potential target genes may change with SARS-CoV-2 infection, thus it may help to molecularly explain the effect of SARS-CoV-2 infection on the testis in men.

Keywords

• COVID-19
• cell cycle
• testis
• microRNA

Erkek Üreme Sisteminde SARS-CoV-2 RNA’sını Hedefleyen miRNA’ların ve Potansiyel Hedef Genlerinin İn Silico Olarak Belirlenmesi

Abstract

Amaç: Dünya genelinde milyonlarca mortalite ve morbiditeye neden olan SARS-CoV-2 enfeksiyonu insanlarda moleküler düzeyde çok sayıda farklı patolojiye sebep olmuştur. Yapılan çalışmalar bu virüsün erkek üreme hücreleri üzerine etkili olabileceğini göstermiştir. Bu çalışmada, SARS-CoV-2 enfeksiyonunun miRNA’lar aracılığı ile infertiliteye nasıl sebep olabileceğinin in silico araştırılması amaçlandı. Gereç ve Yöntemler: Sağlıklı testis dokusunda en yüksek oranda ifade edilen miRNA’lar Tissue Atlas'tan elde edildi. Bu miRNA’lar arasından COVID-19 RNA’sını hedeflediği belirlenen miRNA’lar miRDB veri tabanından listelendi. Elde edilen liste makine öğrenimi algoritmasını kullanan miRWalk veri tabanı ile karşılaştırıldı. Ortak hedefler deneysel olarak doğrulanmış miRNA-hedef etkileşimleri veri tabanı olan miRTarBase ve sonrasında TargetScan ile eşleştirildi. Bulgular: COVID-19 RNA dizisini hedefleyen ve in silico olarak endojen seviyelerinin etkilendiği tespit edilen testis dokusuna özgü miRNA’lar belirlendi. Bunlardan hsa-miR-195-5p, hsa-miR-16-5p, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-497-5p ve hsa-miR-424-5p’nin mir-15/16 ailesinin, hsa-miR-30c-5p, hsa-miR-30b-5p, hsa-miR-30a-5p’nin ise mir-30 ailesinin üyeleri olduğu ortaya çıkarıldı. Bu miRNA’ların potansiyel hedef genlerinin arasında hücre döngüsü başta olmak üzere, DNA hasarı, apoptoz, spermatogenez ve viral cevapla ilgili olan ABL2, BCL2, PLEKHA1, WNK3, CCNT2, DICER1, CCND1, CCND2, CCND3 ve WEE1 genlerinin olduğu gösterildi. Sonuç: Bu çalışma SARS-CoV-2 enfeksiyonu ile beraber testis dokusuna özgü miRNA’ların ve potansiyel hedef genlerinin ifadesinin değişebileceğini göstermektedir, böylece SARS-CoV-2 enfeksiyonunun erkeklerde testis üzerine etkisini moleküler olarak açıklamaya yardımcı olabilir.

Keywords

• COVID-19
• testis
• hücre siklusu
• mikroRNA

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