Increased HAGLR expression promotes non–small cell lung cancer proliferation and invasion via enhanced de novo lipogenesis

Abstract

Lung cancers are broadly classified into small cell lung cancer and non–small cell lung cancer, with non–small cell lung cancer one of the leading causes of cancer-associated deaths worldwide. Presently, the mechanisms underlying lung tumorigenesis remain incompletely understood. Accumulating evidence indicates that abnormal expression of long non-coding RNAs is associated with tumorigenesis in multiple cancers, including lung cancer. HAGLR messenger RNA of non–small cell lung cancer tissues was significantly higher. Moreover, high levels of HAGLR expression were associated with non–small cell lung cancer tumor lymph node metastasis status, stage, and poor overall survival. Inhibition of HAGLR in non–small cell lung cancer cells suppressed cell proliferation and invasion. RNA interference–mediated downregulation of HAGLR also decreased levels of fatty acid synthase, with fatty acid synthase levels positively correlated with HAGLR expression in non–small cell lung cancer specimens. In addition, the cellular free fatty acid content of cancer cells was decreased following HAGLR knockdown. HAGLR depletion significantly inhibited the growth of non–small cell lung cancer cells in vivo. Furthermore, the expression levels of p21 and matrix metallopeptidase-9 (MMP-9) were dysregulated when HAGLR expression was suppressed. Our results suggest that HAGLR is an important regulator of non–small cell lung cancer cell proliferation and invasion, perhaps by regulating fatty acid synthase. Therefore, targeting HAGLR may be a possible therapeutic strategy for non–small cell lung cancer.