Long noncoding RNA SOX21-AS1 promotes cervical cancer progression by competitively sponging miR-7/VDAC1

J Cell Physiol. 2019 Aug;234(10):17494-17504. doi: 10.1002/jcp.28371. Epub 2019 Mar 25.

Abstract

Growing evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in cervical cancer. Dy000sregulation of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) has been reported in several tumors. However, its expression pattern and potential biological function in cervical cancer (CC) have not been investigated. In this study, we first reported that SOX21-AS1 expression was significantly upregulated in both CC tissues and cell lines. High expression of SOX21-AS1 was found to be significantly correlated with Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and depth of cervical invasion. Further clinical assay confirmed that high SOX21-AS1 expression was associated with shorter overall survival and could be used as a potential prognostic biomarker for CC patients. Functional investigation showed that knockdown of SOX21-AS1 suppressed CC cells proliferation, migration, and invasion, as well as epithelial to mesenchymal transition progress. Furthermore, our data showed that microRNA-7 (miR-7) interacted with SOX21-AS1 by directly targeting the miRNA-binding site in the SOX21-AS1 sequence, and quantitative real-time polymerase chain reaction results showed overexpression of SOX21-AS1 decreased the levels of miR-7 in CC cells. Moreover, we confirmed that miR-7 directly targeted the 3'-untranslated region of voltage dependent anion channel 1 (VDAC1). Final in vitro assay suggested that in CC cells with SOX21-AS1, VDAC1 overexpression resulted in an increase of cell proliferation, migration, and invasion. Overall, our findings illuminate how SOX21-AS1 formed a regulatory network to confer an oncogenic function in CC and SOX21-AS1 could be regarded as an efficient therapeutic target and potential biomarker for CC patients.

Keywords: SOX21-AS1; VDAC1; cervical cancer; lncRNA; miR-7; prognosis; progression.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • RNA, Antisense / antagonists & inhibitors
  • RNA, Antisense / genetics*
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • SOXB2 Transcription Factors / antagonists & inhibitors
  • SOXB2 Transcription Factors / genetics*
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Voltage-Dependent Anion Channel 1 / genetics*

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • MIRN7 microRNA, human
  • MicroRNAs
  • RNA, Antisense
  • RNA, Long Noncoding
  • SOX21 protein, human
  • SOXB2 Transcription Factors
  • VDAC1 protein, human
  • Voltage-Dependent Anion Channel 1