Int J Biol Sci 2020; 16(11):1989-2000. doi:10.7150/ijbs.43062

Research Paper

Long noncoding RNA MYLK-AS1 promotes growth and invasion of hepatocellular carcinoma through the EGFR/HER2-ERK1/2 signaling pathway

Juan Liu1,2, Si-yuan Zhao3, Qiwei Jiang1, Yuanyuan Qu2, Xiaomei Huang2, Jundong Du4✉, Wanjun Sun2✉, Qinong Ye1✉

1. Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
2. Department of Hematology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China.
3. Medical unit, 91638 Troops, PLA, Beijing 102202, China.
4. Department of Surgery, Hebei Yanda Hospital, Hebei 065201, China.

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Citation:
Liu J, Zhao Sy, Jiang Q, Qu Y, Huang X, Du J, Sun W, Ye Q. Long noncoding RNA MYLK-AS1 promotes growth and invasion of hepatocellular carcinoma through the EGFR/HER2-ERK1/2 signaling pathway. Int J Biol Sci 2020; 16(11):1989-2000. doi:10.7150/ijbs.43062. Available from http://www.ijbs.com/v16p1989.htm

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Abstract

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 in vitro. Consistently, MYLK-AS1 knockdown hinders tumor growth in vivo. 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.

Keywords: LncRNA, MYLK-AS1, hepatocellular carcinoma, EGFR, HER2