Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
Department of Hematology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China.
Int J Biol Sci. 2020 Apr 27;16(11):1989-2000. doi: 10.7150/ijbs.43062. eCollection 2020.
The epidermal growth factor receptor (EGFR) family members EGFR and HER2 play pivotal roles in oncogenesis and tumor progression. Anticancer drugs targeting EGFR and HER2 have been developed. Long noncoding RNAs (lncRNAs) have been reported to regulate cancer development and progression through signaling pathways. However, lncRNAs that regulate EGFR and HER2 expression remain unknown. Here, we show that lncRNA myosin light chain kinase-antisense RNA 1 (MYLK-AS1) promotes EGFR and HER2 expression and activates their downstream signaling pathway. MYLK-AS1 increases hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion . Consistently, MYLK-AS1 knockdown hinders tumor growth . Mechanistically, MYLK-AS1 enhances HCC cell proliferation, migration, and invasion through stimulating the EGFR/HER2-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In addition, MYLK-AS1 is overexpressed in HCC patients and negatively correlated with HCC prognosis. Thus, MYLK-AS1 is an upstream regulator of EGFR/HER2, and acts as an oncogene, suggesting an additional target for cancer therapeutics.
表皮生长因子受体(EGFR)家族成员 EGFR 和 HER2 在肿瘤发生和肿瘤进展中起关键作用。已经开发出针对 EGFR 和 HER2 的抗癌药物。长链非编码 RNA(lncRNA)已被报道通过信号通路调节癌症的发生和发展。然而,调节 EGFR 和 HER2 表达的 lncRNA 仍然未知。在这里,我们表明肌球蛋白轻链激酶反义 RNA 1(MYLK-AS1)促进 EGFR 和 HER2 的表达并激活其下游信号通路。MYLK-AS1 增加肝癌(HCC)细胞的增殖、迁移和侵袭。一致地,MYLK-AS1 敲低抑制肿瘤生长。机制上,MYLK-AS1 通过刺激 EGFR/HER2-细胞外信号调节激酶 1/2(ERK1/2)信号通路来刺激 HCC 细胞的增殖、迁移和侵袭。此外,MYLK-AS1 在 HCC 患者中过度表达,并与 HCC 预后呈负相关。因此,MYLK-AS1 是 EGFR/HER2 的上游调节剂,作为一种癌基因,提示癌症治疗的另一个靶点。