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NKX2-1-AS1 negatively regulates CD274/PD-L1, cell-cell interaction genes, and limits human lung carcinoma cell

Hasmeena Kathuria1, Guetchyn Millien1, Liam McNally1

  • 1The Pulmonary Center, Boston University School of Medicine, 72 E. Concord St, Boston, MA, 02118, USA.

Scientific Reports
|September 28, 2018
PubMed

Insights

Long noncoding RNA NKX2-1-AS1 is elevated in lung cancer and independently regulated. It limits cell migration and immune evasion by downregulating PD-L1, suggesting a role in controlling lung carcinoma progression.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
  • The human antisense lncRNA-NKX2-1-AS1 is located near the NKX2-1 gene on chromosome 14q13.3, a region implicated in cancer progression.

Purpose of the Study:

  • To investigate the role of lncRNA-NKX2-1-AS1 in lung adenocarcinoma.
  • To determine the regulatory relationship between NKX2-1-AS1, NKX2-1, and cancer-related pathways.

Main Methods:

  • Quantitative PCR to measure NKX2-1-AS1 and NKX2-1 levels.
  • Loss-and-gain of function experiments (knockdown and overexpression).
  • Reporter assays to assess promoter activity and protein-DNA interactions.

Main Results:

  • NKX2-1-AS1 and NKX2-1 are upregulated in lung adenocarcinomas but independently regulated.
  • NKX2-1-AS1 knockdown upregulates genes in cell adhesion and PD-L1/PD-1 pathways.
  • NKX2-1-AS1 negatively regulates PD-L1 expression and cell migration, potentially via interaction with NKX2-1 protein.

Conclusions:

  • NKX2-1-AS1 acts independently of NKX2-1 to regulate genes in trans, including PD-L1.
  • NKX2-1-AS1 may limit lung carcinoma cell motility and immune evasion, presenting a novel therapeutic target.

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