LncRNA HOXC-AS1 promotes nasopharyngeal carcinoma (NPC) progression by sponging miR-4651 and subsequently upregulating FOXO6

J Pharmacol Sci. 2021 Nov;147(3):284-293. doi: 10.1016/j.jphs.2021.08.002. Epub 2021 Aug 17.

Abstract

The incidence rate of nasopharyngeal carcinoma (NPC) is the highest among the malignant tumors of otorhinolaryngology, posing a huge burden to public health. Long noncoding RNAs (lncRNAs) exert an important role in tumorigenesis and the progression of various cancers. The present study found that HOXC-AS1 was highly expressed in NPC and in NPC cell lines, suggesting a critical role of HOXC-AS1 in NPC progression. In addition, the abundance of HOXC-AS1 was negatively correlated with the prognosis of NPC. To molecularly dissect the mechanism of HOXC-AS1 in NPC progression, we knocked down the expression of HOXC-AS1 in HNE1 and C666-1 cells. Then, we employed CCK8, colony-formation experiment and Transwell to investigate how the cell performed when HOXC-AS1 was knocked down. It could be observed that HOXC-AS1 knockdown decreases cell proliferation, migration and invasion, but induces cell apoptosis in NPC. We found that HOXC-AS1 could sponge miR-4651 subsequently binding FOXO6 and inhibiting its expression. Therefore, HOXC-AS1/miR-4651/FOXO6 may form a competing endogenous RNA (ceRNA) network that promotes NPC progression. In conclusion, our study demonstrates that HOXC-AS1 promotes NPC progression by sponging miR-4651 and regulating FOXO6 expression, thus providing potential pharmaceutical targets for developing new NPC treatments.

Keywords: FOXO6; HOXC-AS1; Nasopharyngeal carcinoma (NPC); lncRNA; miR-4651.

MeSH terms

  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology*
  • Carcinoma / genetics*
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology*
  • RNA, Long Noncoding / physiology*
  • Up-Regulation / genetics*

Substances

  • FOXO6 protein, human
  • Forkhead Transcription Factors
  • MIRN4651 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding