Expression of microRNA-18a and microRNA-18b in the microenvironment of high-grade Cervical Intraepithelial Neoplasia (CIN2-3)

Abstract

Cervical cancer is ranked as the fourth most common cancer worldwide, and the second leading cause of mortality among young woman 19 – 39 of age. Cervical cancer arises from persistent human papilloma (HPV) infection and may take several years to develop. Because of organized screening a premalignant condition of the disease, Cervical Intraepithelial Neoplasia (CIN), can be detected and treated before it becomes invasive and metastatic. microRNA (miRNA) are defined as a class of small non-coding regulatory RNAs, approximately 22 nucleotides long. The miRNAs interferes with the post-transcriptional regulation of gene expression by base-pairing with the 3`-untranslated region of target messenger RNA. MiR-18a is a member of the miR-17-92 cluster which has been found to be a modulator of effector and memory T-cells. In addition, miR-18a and miR-18b have been found to play a role in development of estrogen receptor alpha (ER-α) negative breast cancer. The aim of this thesis was to optimize methods for isolation, purification and detection of miR-18a and miR-18b in FFPE cervical specimens. The expression of miR-18a and -18b in persistent HPV-16 positive CIN3 samples and normal cervical samples were compared by the use of RT-qPCR and semi-quantitative scoring with CISH. We found that miR-18a and miR-18b were highly expressed in CIN3 lesions as compared to normal cervical tissue. This might show that high expression of these miRNAs, is a sign of poor prognosis of a lesion with potential to developing into cancer. A comparison between CD8+ T-cells and miR-18a expression indicated a possible relationship between these cytotoxic T-cells and and the miR-18a.