Long noncoding RNA HOXC-AS3 enhances the progression of cervical cancer via activating ErbB signaling pathway

J Mol Histol. 2021 Oct;52(5):991-1006. doi: 10.1007/s10735-021-10007-z. Epub 2021 Aug 13.

Abstract

Emerging evidence reveals that long noncoding RNAs (lncRNAs) contribute to human tumorigenesis. Nevertheless, the function of HOXC cluster antisense RNA 3 (HOXC-AS3) in human cervical cancer (CC) remains largely unknown. The levels of HOXC-AS3, miR-105-5p and SOS1 in CC tissues and cells were monitored by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Gain- and loss-of-function experiments were conducted to verify the function of HOXC-AS3 and miR-105-5p in CC cells. Meanwhile, cell proliferation, apoptosis, migration and invasion were examined by the cell counting kit-8 (CCK8) experiment, colony formation assay, flow cytometry and Transwell assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to test the regulatory interaction of HOXC-AS3, miR-105-5p and SOS1. In addition, in vivo experiment was performed to certain the role of HOXC-AS3 in tumorigenesis of CC. HOXC-AS3 was overexpressed in CC tissues (vs. adjacent normal tissues) and CC cells. Besides, the higher HOXC-AS3 profile was associated with the poorer clinical prognosis of CC patients. Overexpression of HOXC-AS3 promoted cell growth, migration and invasion, hampered apoptosis, whereas knocking down HOXC-AS3 exhibited the reverse effects. MiR-105-5p was a downstream target of HOXC-AS3, and it mediated the HOXC-AS3-induced oncogenic effects. Mechanistically, the bioinformatic analysis illustrated that SOS1 was targeted by miR-105-5p. Up-regulating SOS1 heightened the growth, migration and invasion of CC cells by enhancing the ErbB signaling pathway, which was reversed by miR-105-5p. Up-regulated HOXC-AS3 aggravates CC by promoting SOS1 expression via targeting miR-105-5p.

Keywords: Cervical cancer; ErbB signaling pathway; HOXC cluster antisense RNA 3; Sevenless Homolog 1; miR-105-5p.

MeSH terms

  • Animals
  • Base Sequence
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Disease Progression*
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Metastasis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • SOS1 Protein / metabolism
  • Signal Transduction*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • MIRN105 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SOS1 Protein
  • SOS1 protein, human
  • ErbB Receptors