A novel lncRNA, Lnc21q22.11, suppresses gastric cancer growth by inhibiting MEK/ERK pathway.

Abstract

Gastric cancer (GC) is one of the most common malignancies with limited treatment options and poor prognosis. Therefore, it is necessary to identify new markers for the development of novel therapeutic strategies. Long non-coding RNAs (lncRNAs) have emerged as pivotal players in cancer. However, RNA-based cancer therapy has been challenged by non-specificity and adverse immune effects. Thus, a comprehensive understanding of the functional roles of lncRNAs and their regulatory networks in downstream pathways may provide more specific targets. In this study, we identified a novel lncRNA, Lnc21q22.11, encoded by the region of chromosome 21q22.11. The full-length transcript was 1202 nt, and its expression was reduced in GC. The expression of Lnc21q22.11 was regulated by histone methylation. Lnc21q22.11 inhibited GC cell proliferation, colony formation, invasion, and migration. Lnc21q22.11 suppressed N87 cell xenograft growth in mice. Mechanistically, Lnc21q22.11 inhibited the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathway by interacting with MYH9 in GC cells. Loss of or reduced Lnc21q22.11 expression sensitized GC cells to MEK inhibitor. In conclusion, Lnc21q22.11 is a novel lncRNA in gastric cancer. It suppresses gastric cancer growth by inhibiting the MEK/ERK signaling pathway both in vitro and in vivo.