Long non-coding RNA HOXA11 antisense RNA upregulates spermatogenesis-associated serine-rich 2-like to enhance cisplatin resistance in laryngeal squamous cell carcinoma by suppressing microRNA-518a

Bioengineered. 2022 Jan;13(1):974-984. doi: 10.1080/21655979.2021.2016038.

Abstract

Long noncoding RNAs (LncRNAs) are closely associated with the chemoresistance of laryngeal squamous cell carcinoma (LSCC). Previous studies indicated that HOXA11-AS could function as a vital regulator in human cancers. However, the regulatory mechanisms of HOXA11-AS in the chemoresistance of LSCC remain unclear. In this study, it was found that HOXA11-AS expression was upregulated in cisplatin (CDDP)-resistant LSCC tissues and cells. Loss-of-function assays revealed that HOXA11-AS knockdown inhibited the viability, migration, and invasion, but promoted the apoptosis of CDDP-resistant LSCC cells. Meanwhile, we identified miR-518a as a downstream gene of HOXA11-AS in LSCC, and miR-518a silencing reversed the promotive effect of HOXA11-AS knockdown on CDDP sensitivity of LSCC cells. In addition, miR-518a could inhibit spermatogenesis-associated serine-rich 2-like (SPATS2L) expression by direct interaction, and upregulation of SPATS2L abrogated the inhibitory effect of HOXA11-AS silencing or miR-518a overexpression on CDDP resistance of CDDP-resistant LSCC cells. In sum, our results demonstrated that HOXA11-AS enhanced CDDP resistance of LSCC via miR-518a/SPATS2L axis, which might offer novel therapeutic strategies for CDDP-resistant LSCC.

Keywords: HOXA11-AS; SPATS2L; laryngeal squamous cell carcinoma; miR-518a.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laryngeal Neoplasms / genetics*
  • MicroRNAs / genetics*
  • Proteins / genetics*
  • RNA, Long Noncoding / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Up-Regulation

Substances

  • MIRN518 microRNA, human
  • MicroRNAs
  • Proteins
  • RNA, Long Noncoding
  • SPATS2L protein, human
  • Cisplatin

Grants and funding

This study was supported by Key Science and Technology Research Project of Health Commission of Hebei Province [20180794].