Novel insights into the mechanisms by which lncRNA HOTAIR regulates migration and invasion in HeLa cells

Cell Cycle. 2022 Mar-Mar;21(6):602-617. doi: 10.1080/15384101.2022.2030167. Epub 2022 Jan 28.

Abstract

HOTAIR, as one of the few well-studied oncogenic lncRNAs, is involved in human tumorigenesis and is dys-regulated in most human cancers. The transcription co-activator factor YAP1 is broadly expressed in many tissues, and promotes cancer metastasis and progression. However, the precise biological roles of HOTAIR and YAP1 in cancer cells remain unclear. In this study, we showed that HOTAIR regulates H3K27 histone modification in the promoter of miR-200a to mediate miR-200a expression by recruiting EZH2. YAP1, as a potential target gene of miR-200a, aggravated the effects of miR-200a on the migration and invasion of HeLa cells. YAP1 activated the transcription of RPL23, which is a novel downstream transcriptional-regulator of YAP1. Agreement with this, the expression of YAP1 and RPL23 was dramatically decreased after injecting HeLa cells transfected with siHOTAIR in a xenograft mouse model. Accordingly, we propose a novel model of the molecular mechanism by which HOTAIR promotes the migration and invasion of cancer cells involving the miR-200a-3p/YAP1/RPL23 axis.

Keywords: HOTAIR; RPL23; YAP1; invasion; lncRNA; miR-200a; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • HOTAIR long untranslated RNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors

Grants and funding

This work was supported by the National Natural Science Foundation of China (NO. 31500622, 31970367), the program of Wuhan University of Science and technology (NO. 25011401).