Natural Antisense Long Noncoding RNA HHIP-AS1 Suppresses Non-Small-Cell Lung Cancer Progression by Increasing HHIP Stability via Interaction with CELF2

Crit Rev Eukaryot Gene Expr. 2022;33(1):67-77. doi: 10.1615/CritRevEukaryotGeneExpr.2022043174.

Abstract

Non-small-cell lung cancer (NSCLC) is a major category of lung cancer, with high incidence and high mortality. Natural antisense long noncoding RNAs (lncRNAs) are involved in the development of NSCLC via their regulation of biological processes. However, the function of the lncRNA Hedgehog-interacting protein antisense RNA 1 (HHIP-AS1) in NSCLC is mostly unknown. In the study discussed here, HHIP-AS1 and HHIP levels were predicted based on the TCGA database, and detected via qRT-PCR or western blotting assays. Cell proliferation, migration, and invasion were measured via CCK-8 and trans-well assays. Related protein levels were measured using western blotting analysis. The results showed that HHIP-AS1 and HHIP levels are downregulated in NSCLC, and that low HHIP-AS1 and HHIP expression is associated with poor outcomes. HHIP-AS1 overexpression represses cell proliferation, migration, and invasion in NSCLC. HHIP-AS1 enhances HHIP expression and stability, and this effect is mediated by CELF2. HHIP silencing attenuates the suppressive roles of HHIP-AS1 in proliferation, migration, and invasion. As a result of these findings, it is concluded that HHIP-AS1 overexpression restrains proliferation, migration, and invasion of NSCLC cells by increasing HHIP stability via its targeting of CELF2.

MeSH terms

  • CELF Proteins / genetics
  • CELF Proteins / metabolism
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • MicroRNAs* / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • Hedgehog Proteins
  • MicroRNAs
  • CELF2 protein, human
  • CELF Proteins
  • Nerve Tissue Proteins
  • HHIP protein, human
  • Carrier Proteins
  • Membrane Glycoproteins