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

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 <i>in vitro</i> and <i>in vivo</i>. • Lnc21q22.11 is a novel lncRNA with the full length obtained. • The expression of Lnc21q22.11 is regulated by histone modification. • Lnc21q22.11 suppresses gastric cancer growth both <i>in vitro</i> and <i>in vivo</i>. • Lnc21q22.11 inhibits MEK/ERK signaling pathway by interacting with MYH9.

胃癌（Gastric cancer，GC）是最常见的恶性肿瘤之一，治疗选择有限且预后不良。因此，亟需发现新的标志物以开发新型治疗策略。长链非编码RNA（Long non-coding RNA，lncRNA）已成为癌症发生发展中的关键调控因子。然而，基于RNA的癌症治疗面临非特异性和不良免疫效应的挑战。因此，全面解析lncRNA的功能及其在下游通路中的调控网络，或可为治疗提供更具特异性的靶点。本研究中，我们发现了一种新型lncRNA——Lnc21q22.11，其编码区域位于21号染色体21q22.11区。该lncRNA的全长转录本为1202核苷酸（nt），且在胃癌中表达下调。Lnc21q22.11的表达受组蛋白甲基化调控。Lnc21q22.11可抑制胃癌细胞增殖、集落形成、侵袭及迁移。Lnc21q22.11可抑制小鼠体内N87细胞异种移植瘤的生长。机制研究表明，Lnc21q22.11通过与MYH9相互作用，抑制胃癌细胞中丝裂原活化蛋白激酶激酶/细胞外信号调节激酶（mitogen-activated protein kinase kinase/extracellular signal-regulated kinase，MEK/ERK）信号通路。Lnc21q22.11表达缺失或下调可增强胃癌细胞对MEK抑制剂的敏感性。综上，Lnc21q22.11是一种新型胃癌相关lncRNA，通过抑制MEK/ERK信号通路在体内外发挥胃癌生长抑制作用。
• Lnc21q22.11是一种新型lncRNA，其全长序列已被解析。
• Lnc21q22.11的表达受组蛋白修饰调控。
• Lnc21q22.11在体内外均可抑制胃癌生长。
• Lnc21q22.11通过与MYH9相互作用抑制MEK/ERK信号通路。