Alternative variants of interleukin-2 receptor alpha chain mRNA in colon cancer

• Novikov V.V.
• Shumilova S.V.
• Novikov D.V.
• Alyasova A.V.
• Irina V. Evsegneeva
• Alexander V. Karaulov

Abstract

Introduction. The alpha chain of the interleukin-2 receptor is encoded by a full-length mRNA which has several alternatively spliced variants whose function is unknown. Information on the occurrence of alternatives to mRNA alpha chain IL-2R in colon cancer help establish their role in antitumor immunity mechanisms.

The aim of the study was to detect the content of soluble CD25 molecules, a full-length form of IL-2Rα mRNA (CD25 mRNA) encoding a functionally active receptor alpha-chain and a form with 4 exon deletion (CD25Exo4Del mRNA) and 4 and 5 exons deletion (CD25Exo4-5Del mRNA) encoding a protein unable to bind interleukin-2. In the blood of healthy individuals and in the blood and tumors of colon cancer patients and compare the expression of IL-2Rα mRNA alternative forms with an expression of the genes coding CD38, ICAM-1, Fas and several cancer-testicular antigens (MAGEA1-MAGEA6, CT7 (MAGEC1), GAGE1-GAGE8, NY-ESO-1, SSX1, 2, 4, TRAG3 and XAGE1) expression.

Material and methods. 49 tumor samples and 10 peripheral blood samles of colon cancer are used in the work. The study was carried out by a reverse transcription polymerase chain reaction.

Results. It was shown that three alternative forms of mRNA IL-2Rα present in the blood of both healthy individuals and patients with colon cancer. In tumors, alternative mRNAs of IL-2Rα were detected with different frequencies. Full-length mRNA was detected most often, CD25Exo4Del mRNA - with an intermediate frequency and CD25Exo4-5Del mRNA - most rarely. There was a tendency to decrease the frequency of CD25Exo4-5Del mRNA detection in the late stages of the disease. ICAM-1 expression frequency in mRNA CD25Exo4-5Del negative tumors was increased, and soluble CD25 molecules serum level in the absence of CD25Exo4Del mRNA in tumor was also increased.

Сonclusion. The regulatory role of IL-2Rα mRNA deleted forms products leading to regulatory T cells activation, immunosuppression increasing and tumor growth progression was established.

Keywords:interleukin-2 receptor alpha-chain; mRNA alternative variants; colon cancer; regulatory T cells

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