LncRNA MIR31HG fosters stemness malignant features of non-small cell lung cancer via H3K4me1- and H3K27Ace-mediated GLI2 expression

Oncogene. 2024 May;43(18):1328-1340. doi: 10.1038/s41388-023-02883-4. Epub 2023 Nov 10.

Abstract

Non-coding RNAs are responsible for oncogenesis and the development of stemness features, including multidrug resistance and metastasis, in various cancers. Expression of lncRNA MIR31HG in lung cancer tissues and peripheral sera of lung cancer patients were remarkably higher than that of healthy individuals and indicated a poor prognosis. Functional analysis showed that MIR31HG fosters stemness-associated malignant features of non-small cell lung cancer cells. Further mechanistic investigation revealed that MIR31HG modulated GLI2 expression via WDR5/MLL3/P300 complex-mediated H3K4me and H3K27Ace modification. In vivo MIR31HG repression with an antisense oligonucleotide attenuated tumor growth and distal organ metastasis, whereas MIR31HG promotion remarkably encouraged cellular invasion in lung and liver tissues. Our data suggested that MIR31HG is a potential diagnostic indicator and druggable therapeutic target to facilitate multiple strategic treatments for lung cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Lysine / analogs & derivatives*
  • Male
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • Zinc Finger Protein Gli2* / genetics
  • Zinc Finger Protein Gli2* / metabolism

Substances

  • RNA, Long Noncoding
  • Zinc Finger Protein Gli2
  • GLI2 protein, human
  • Histones
  • Nuclear Proteins
  • WDR5 protein, human
  • (histone H3)-N6-methyl-L-lysine-4
  • Lysine
  • Intracellular Signaling Peptides and Proteins