Long noncoding RNA MALAT1 promotes the stemness of esophageal squamous cell carcinoma by enhancing YAP transcriptional activity

FEBS Open Bio. 2019 Aug;9(8):1392-1402. doi: 10.1002/2211-5463.12676. Epub 2019 Jun 11.

Abstract

The tumor promoting roles of long noncoding RNA (lncRNA) MALAT1 have been revealed in various cancers; however, its roles in esophageal squamous cell carcinoma (ESCC) have not previously been disclosed. In this study, we found that MALAT1 expression was remarkably increased in ESCC cells compared to normal human esophageal epithelial cells. In addition, knockdown of MALAT1 attenuated the stemness of ESCC cells, as evidenced by a decrease in spheroid formation capacity, stemness marker expression and aldehyde dehydrogenase 1 activity. Moreover, MALAT1 knockdown decreased the migration ability of ESCC cells. Notably, knockdown of MALAT1 enhanced the radiosensitivity and chemosensitivity of ESCC cells. We also established that MALAT1 binds directly to Yes-associated protein (YAP), thereby enhancing YAP protein expression and increasing YAP transcriptional activity. Overexpression of YAP partially rescued the effect of MALAT1 knockdown on stemness and radiosensitivity of ESCC cells. Overall, this study has identified that a novel MALAT1-YAP axis promotes the stemness of ESCC cells, and thus could be a potential target for treatment of ESCC.

Keywords: MALAT1; YAP; esophageal squamous cell carcinoma; migration; stemness.

Publication types

  • Retracted Publication

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Humans
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • Cell Cycle Proteins
  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Transcription Factors
  • YY1AP1 protein, human