HMGA1-Regulating microRNAs Let-7a and miR-26a are Downregulated in Human Seminomas

HMGA1 调节的 microRNA Let-7a 和 miR-26a 在人类精原瘤中下调

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作者:Marco De Martino, Francesco Esposito, Simona Pellecchia, Ricardo Cortez Cardoso Penha, Gerardo Botti, Alfredo Fusco, Paolo Chieffi

Background

Recent studies have underlined HMGA protein's key role in the onset of testicular germ cell tumors, where HMGA1 is differently expressed with respect to the state of differentiation, suggesting its fine regulation as master regulator in testicular tumorigenesis. Several studies have highlighted that the HMGA1 transcript is strictly regulated by a set of inhibitory microRNAs. Thus, the

Conclusions

these data strongly support that the upregulation of HMGA1 levels occurring in seminoma is-at least in part-due to the downregulation of HMGA1-targeting microRNAs.

Methods

HMGA1 mRNA and Let-7a and miR-26a levels were measured in a seminoma dataset available in the Cancer Genome Atlas database and confirmed in a subset of seminomas by qRT-PCR and western blot. A TCam-2 seminoma cell line was then transfected with Let-7a and miR-26a and tested for proliferation and motility abilities.

Results

an inverse correlation was found between the expression of miR-26a and Let-7a and HMGA1 expression levels in seminomas samples, suggesting a critical role of these microRNAs in HMGA1 levels regulation. Accordingly, functional studies showed that miR-26a and Let-7a inhibited the proliferation, migration and invasion capabilities of the human seminoma derived cell line TCam-2. Conclusions: these data strongly support that the upregulation of HMGA1 levels occurring in seminoma is-at least in part-due to the downregulation of HMGA1-targeting microRNAs.

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