LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p/HOXA3 Axis

Hum Gene Ther. 2019 May;30(5):618-631. doi: 10.1089/hum.2018.109. Epub 2019 Feb 26.

Abstract

The long non-coding RNA HOXA-AS2 has been found to be an oncogene in several types of human malignant tumors. However, its role in regulating the occurrence and development of papillary thyroid cancer (PTC) is still unclear. The present study investigated the function and mechanism(s) of HOXA-AS2 in PTC progression. Using quantitative real-time polymerase chain reaction, HOXA-AS2 was found to be differentially expressed in PTC tissues and cell lines. Kaplan-Meier analysis indicated that the overall survival rate of patients with higher levels of HOXA-AS2 was lower than those with relatively lower levels. Loss-of-function assays revealed that HOXA-AS2 knockdown inhibited PTC progression by inhibiting cellular proliferation, migration, and invasion and accelerating apoptosis. Mechanistically, loss-of-function assays showed a positive correlation between HOXA3 and HOXA-AS2 expression. Subcellular fractionation assay results revealed abundant HOXA-AS2 expression in the cytoplasm of PTC cells. Additionally, FOXD2-AS1 was found to upregulate HOXA3 expression by binding to miR-15a-5p. Finally, rescue assays demonstrated the overall function of the HOXA-AS2/miR-15a-5p/HOXA3 axis in PTC progression. These findings will significantly contribute to further research and the development of more efficient treatments for thyroid cancer in the future.

Keywords: HOXA-AS2; HOXA3; Wnt/β-catenin signaling pathway; miR-15a-5p; papillary thyroid cancer.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Biomarkers, Tumor
  • Carcinogenesis / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Genes, Reporter
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / mortality
  • Thyroid Cancer, Papillary / pathology*

Substances

  • Biomarkers, Tumor
  • HOXA3 protein, human
  • Homeodomain Proteins
  • MIRN15 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long noncoding RNA HOXA-AS2, human