Upregulation of Microrna-106a is Associated with Microsatellite Instability Status in Colorectal Cancer

Abstract

Microsatellite instability (MSI) is a genetic condition that results from errors in DNA repair genes and causes colorectal cancer (CRC). The incidence of MSI in sporadic CRCs and its effect on prognosis are contradictory in the literature. However, since standard chemotherapy is insufficient in CRCs with MSI, new treatment options are needed. micoRNAs (miRNAs) are small RNA molecules that take part in the cancer process and are used as markers in diagnosis, prognosis and treatment. In the study, it is aimed to define the prevalence of MSI in sporadically developing CRCs belonging to the Turkish population and to determine the expression differences of miRNAs in these tumors. 63 patients diagnosed with sporadic CRC were evaluated in the study. DNA and RNA isolations were made from archive tumor and normal tissues of the patients. MSI test was performed based on fragment analysis from DNA samples. The expression profiles of 38 different miRNAs were examined using qRT-PCR. In 63 patients, the incidence of MSI was determined as 23.8%. When MSI and microsatellite stable (MSS) tumors were compared, it was determined that miR-124 and miR-106a showed high expression and miR-145 low expression in MSI tumors (p <0.05). However, high expression of miR-106a was found to be associated with postoperative recurrence (p=0.002). In the light of the findings obtained, we think that by targeting miR-106a especially in CRC tumors with MSI genetype, recurrence can be prevented by creating new treatment protocols in these tumors.

Keywords

• Sporadic colorektal cancer
• Mikrosatellite Instability
• MicroRNA
• miR-106a

MikroRNA-106a’nın Yüksek Ekspresyonu Kolorektal Kanserlerde Mikrosatellit İnstablite Durumu ile İlişkilidir

Abstract

Mikrosatellit instabilite (MSI), DNA tamir genlerindeki hatalardan kaynaklanan ve kolorektal kanserin (KRK) oluşmasına neden olan genetik bir durumdur. Sporadik KRK’larda MSI görülme sıklığı, prognoza olan etkisi literatürde çelişkilidir. Bununla birlikte MSI’ya sahip KRK’larda standart kemoterapi yetersiz kaldığı için yeni tedavi seçeneklerine ihtiyaç duyulmaktadır. micoRNA’lar (miRNA) kanserleşme sürecinde görev alan ve tanıda, prognozda ve tedavide belirteç olarak kullanılan küçük RNA molekülleridir. Mevcut çalışmada, Türk popülasyonuna ait sporadik gelişen KRK’larda MSI’nın görülme sıklığının tanımlanması ve bu tümörlerde miRNA’ların ekspresyon farklılıklarının belirlenmesi amaçlanmıştır. Çalışmada, sporadik KRK tanısı almış 63 hasta değerlendirildi. Hastalara ait arşiv tümör ve normal dokula-rından DNA ve RNA izolasyonları yapıldı. DNA örneklerinden fragment analizine dayalı MSI testi gerçekleştirildi. qRT-PCR kullanılarak 38 farklı miRNA’nın ekspresyon profili incelendi. 63 hastada MSI görülme oranı %23.8 olarak belirlendi. MSI ve mikrosatellit stabil (MSS) tümörler karşılaştırıldığında, MSI tümörlerde, miR-124 ve miR-106a’nın yüksek ve miR-145’in ise düşük ekspresyon gösterdiği belirlendi (p<0.05). Bununla birlikte miR-106a’nın yüksek ekspresyonunun cerrahi sonrası nüks gelişimi ile ilişkili olduğu saptandı (p=0.002). Elde edilen bulgular ışığında miR-106a’nın özellikle MSI genotipine sahip KRK tümörlerde hedeflenmesi ile KRK hastalarında yeni tedavi protokollerinin oluşturularak nüks oluşumunun engellenebileceğini öngörülmüştür.

Keywords

• Sporadik Kolorektal Kanser
• Mikrosatellit İnstability
• MikroRNA
• miR-106a

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