Expressions of miR-30c and let-7a are inversely correlated with HMGA2 expression in squamous cell carcinoma of the vulva.

Antonio Agostini,Sverre Heim,Ioannis Panagopoulos,Francesca Micci,Marta Brunetti,Claes G Trope,Ben Davidson

doi:10.18632/oncotarget.13187

Abstract

Malignant tumors of the vulva, most of them squamous cell carcinomas, account for only 5% of cancers of the female genital tract. Though little is known about the genetic features of these tumors, the Fragile Histidine Triad (FHIT) and High Mobility Group AT-hook 2 (HMGA2) genes were found deregulated. We wanted to gain more knowledge about the expression of HMGA2-related miRNAs such as miR-30c and let-7a, and whether a correlation exists between the expression of FHIT and HMGA2, in this tumor type. An inverse correlation was found in-as-much as HMGA2 was highly expressed (mean fold change 8.8) whereas miR30c and let-7a were both downregulated (mean fold change -3.9 and -2.3, respectively). The consistent overexpression of HMGA2 found in all tumors adds to the likelihood that this gene is of importance in SCC pathogenesis. Moreover, we came to the conclusion that miRNAs may be the cause of the deregulation of HMGA2. Our results also show that SCC of the vulva presents a characteristic molecular pattern with FHIT being downregulated whereas HMGA2 is upregulated.

Highlights

Squamous cell carcinomas (SCC) account for 70% of all malignant tumors arising in the vulva. [1]
HMGA2 was expressed at high levels in all 10 tumors analyzed with an 8.8 fold change average (Figure 1A). miR-30c was strongly downregulated in all 10 tumors (Figure 1B) with an average fold change of -3.9
We found that HMGA2 was expressed at high levels in all 10 vulvar SCC analyzed with an average fold change of 8.8

Summary

Introduction

Squamous cell carcinomas (SCC) account for 70% of all malignant tumors arising in the vulva. [1]. FHIT enhances the expression of miR-30c as well as HMGA2 repression thereby inhibiting epithelialmesenchymal transition and the metastatic process in small cell carcinoma of the lung. The interaction between this miRNA and the HMGA2 3’untranslated region (3’UTR) seems to be crucial in gene expression control [8]. Since our previous findings in SCC of the vulva [2] hint at a similar expression correlation as that detected in lung cancer, we decided to quantify the expression levels of HMGA2 and miR-30c in the 10 tumors of the vulva that were found to have deregulated HMGA2 and FHIT, and to assess the expression levels of the miRNA let-7a which is known to target and repress HMGA2 [9,10,11], as well as the expression of the let-7a regulators LIN28A and LIN28B [12]

Methods

Results

Conclusion