Upregulation of miRNA-10a-5p promotes tumor progression in cervical cancer by suppressing UBE2I signaling

J Obstet Gynaecol. 2023 Dec;43(1):2171283. doi: 10.1080/01443615.2023.2171283.

Abstract

Cervical cancer (CC) is a common malignant neoplasm in gynecology. There is increasing evidence to suggest that microRNAs (miRNAs) act as crucial regulators of CC. However, whether miR-10a-5p plays a role in CC is under investigation. The aim of this stuy was to assess the miR-10a-5p expression pattern in the development of CC and investigate its downstream target. MiR-10a-5p inhibition decreased CC cell proliferation and impaired CC cell invasion and migration but enhanced apoptosis. UBE2I was a direct target of miR-10a-5p. QRT-PCR results showed a down-regulation of UBE2I in CC cells, opposing miR-10a-5p. Besides, overexpression of miR-10a-5p down-regulated UBE2I. Functional rescue experiments further indicated the miR-10a-5p-UBE2I axis was linked to CC cell growth, apoptosis and metastasis. MiR-10a-5p upregulation promotes cervical cancer development by inhibiting UBE2I. These results also predict that miR-10a-5p may be a potential target for the clinical treatment of CC.IMPACT STATEMENTWhat is already known on this subject? As a widely researched cancer-related miRNA, the overexpression of miR-10a-5p has been verified in various cancers. It has been described in a meta-analysis report that there were 42 miRNAs up-regulated and 21 miRNAs down-regulated in different stages of cervical cancer tissue versus healthy tissue.What do the results of this study add? We verified that miR-10a-5p initiates and promotes tumor cell development by decreasing UBE2I abundance. This miR-10a-5p-mediated post-transcriptional regulation of UBE2I is involved in the tumorigenesis, invasion and migration of human cervical cancer.What are the implications of these findings for clinical practice and/or further research? These findings provide mechanistic insights into how miR-10a-5p regulates cervical cancer hyper-proliferation and metastasis, as well as a new target for clinical treatment. Nevertheless, whether miR-10a-5p/UBE2I axis can be regulated by non-invasive methods need further exploration, which will be the focus of our future research.

Keywords: Cervical cancer; UBE2I; epigenetic regulation; metastasis; microRNA (miRNA).

Publication types

  • Meta-Analysis

MeSH terms

  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Signal Transduction / genetics
  • Ubiquitin-Conjugating Enzymes* / genetics
  • Up-Regulation
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / pathology

Substances

  • MicroRNAs
  • MIRN10 microRNA, human
  • ubiquitin-conjugating enzyme UBC9
  • Ubiquitin-Conjugating Enzymes