Circular RNA circ_0011385 promotes cervical cancer progression through competitively binding to miR-149-5p and up-regulating SOX4 expression

Kaohsiung J Med Sci. 2021 Dec;37(12):1058-1068. doi: 10.1002/kjm2.12432. Epub 2021 Aug 9.

Abstract

Circular RNAs (circRNAs), emerging as a new type of non-coding RNAs, play important roles in cancers. Instead, the functions and mechanisms of circ_0011385 in cervical cancer (CC) are still inconclusive. Microarray data GSE102686 was downloaded from Gene Expression Omnibus (GEO) database, and were utilized to screen out circRNAs differently expressed in CC tissues. Circ_0011385, miR-149-5p, SRY-box transcription factor 4 (SOX4) mRNA expressions in CC tissues and cells were probed by quantitative real-time PCR (qRT-PCR). CC cell lines with circ_0011385 knockdown were constructed, and he multiplication, migration, invasion, and apoptosis of CC cells were evaluated by cell counting kit-8 (CCK-8) method, transwell assay, and flow cytometry. In addition, the targeting relationships between miR-149-5p and circ_0011385 or SOX4 mRNA 3'UTR were probed by dual-luciferase reporter gene assay and RNA pull-down assay. The regulatory function of circ_0011385 and miR-149-5p on SOX4 expression was studied with western blot. Expressions of circ_0011385 and SOX4 mRNA were raised in CC tissues and cells, while miR-149-5p expression was decreased. Knocking down circ_0011385 restrained the multiplication, migration, and invasion of CC cells and induced the apoptosis. Circ_0011385 directly targeted miR-149-5p, and SOX4 was the target of miR-149-5p, which could be positively regulated by circ_0011385. Circ_0011385 elevates SOX4 expression by targeting miR-149-5p, thus participating in promoting the malignant biological behaviors of CC cells.

Keywords: SOX4; cervical cancer; circ_0011385; miR-149-5p.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Humans
  • MicroRNAs / physiology*
  • Middle Aged
  • RNA, Circular / physiology*
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / physiology*
  • Uterine Cervical Neoplasms / etiology*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN149 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • SOX4 protein, human
  • SOXC Transcription Factors