Int J Biol Sci 2021; 17(8):1963-1978. doi:10.7150/ijbs.55557

Research Paper

LncRNA EPB41L4A-AS2 represses Nasopharyngeal Carcinoma Metastasis by binding to YBX1 in the Nucleus and Sponging MiR-107 in the Cytoplasm

Mingyu Du1*, Xinyu Hu1,2*, Xuesong Jiang1*, Li Yin1, Jie Chen1, Jing Wen1, Yanxin Fan1, Fanyu Peng1,2, Luxi Qian1,2, Jing Wu1✉, Xia He1✉

1. Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institue of Cancer Research, Nanjing, China.
2. The Fourth Clinical School of Nanjing Medical University, Nanjing, China.
*These authors contributed equally to this work.

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Citation:
Du M, Hu X, Jiang X, Yin L, Chen J, Wen J, Fan Y, Peng F, Qian L, Wu J, He X. LncRNA EPB41L4A-AS2 represses Nasopharyngeal Carcinoma Metastasis by binding to YBX1 in the Nucleus and Sponging MiR-107 in the Cytoplasm. Int J Biol Sci 2021; 17(8):1963-1978. doi:10.7150/ijbs.55557. Available from https://www.ijbs.com/v17p1963.htm

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Abstract

Nasopharyngeal carcinoma (NPC) is known for its potential to progress to the lymph nodes and distant metastases at an early stage. As an important regulator in tumorigenesis biological processes, the functions of lncRNA in NPC tumor development remain largely unclear. In this research, the expression of EPB41L4A-AS2 in NPC tissues and cells was analyzed via real-time quantitative polymerase chain reaction (qRT-PCR). CCK8, colony formation, and EDU experiments were used to determine the viability of NPC cells. Transwell and wound healing assays were performed to test NPC cell migration and invasion. RNA pull-down and mass spectrometry analysis were used to identify potential binding proteins. Then, a popliteal lymph node metastasis model was established to test NPC metastasis. EPB41L4A-AS2 is repressed by transforming growth factor-beta, which is downregulated in NPC cells and tissue. It is associated with the presence of distant metastasis and adverse outcomes. The univariate and multivariate survival assays confirmed that EPB41L4A-AS2 expression was an independent predictor of progression-free survival (PFS) in patients with NPC. Biological analyses showed that overexpression of EPB41L4A-AS2 reduced the metastasis and invasion of NPC in vitro and in vivo, but had no significant effect on cell proliferation. Mechanistically, in the nucleus we identified that EPB41L4A-AS2 relies on binding to YBX1 to reduce the stability of Snail mRNA to enhance the expression of E-cadherin and reverse the progression of epithelial-to-mesenchymal transition (EMT). In the cytoplasm, we found that EPB41L4A-AS2 blocked the invasion and migration of NPC cells by promoting LATS2 expression via sponging miR-107. In a whole, the findings of this study help to further understand the metastasis mechanism of NPC and could help in the prevention and treatment of NPC metastasis.

Keywords: EPB41L4A-AS2, nasopharyngeal carcinoma, YBX1, EMT, miR-107, LATS2