HAGLROS promotes cell proliferation and angiogenesis and inhibits apoptosis by activating multiple signaling pathways in LSCC cells

Background: HAGLROS is a long noncoding RNA involving in the development of a variety of cancers, but its mechanism of action in laryngeal squamous cell carcinomas (LSCC) is still unclear. We aim to unveil the effect and mechanism of HAGLROS on LSCC.

Methods: The expression of HAGLROS in LSCC patients' tissues, serum, and LSCC cell lines was quantified by quantitative real-time PCR. AMC-HN-8 and SNU-46 cells were transfected with the overexpression plasmid of HAGLROS and shHAGLROS, and the functional assay (colony formation assays, flow cytometry, and tube formation) was performed. Western blot was used to determine the expressions of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), P27 and cleaved caspase-3, as well as phosphorylated-c-Jun-N-terminal kinase (p-JNK), JNK, phosphorylated-extracellular signal-regulated kinase 1/2 (p-Erk1/2), Erk1/2, phosphorylated-protein kinase B (p-AKT) and AKT.

Results: HAGLROS was highly expressed in LSCC tissues and cells, and it was correlated to lymph node, tumor depth, and clinical stage of LSCC patients. The proliferation ability of LSCC cells was higher than that of HuLa-PC cells. Meanwhile, HAGLROS overexpression promoted the abilities of proliferation and angiogenesis and reduced apoptosis, whereas silencing of HAGLROS exerted the opposite effects in LSCC cell lines. Moreover, overexpressed HAGLROS upregulated the expressions of VEGF and PCNA yet downregulated the expressions of P27 and cleaved caspase-3 by activating Erk1/2 and AKT or JNK signaling pathways in different LSCC cell lines.

Conclusion: Overexpressed HAGLROS promoted the proliferation and angiogenesis yet inhibited apoptosis of LSCC cells by activating Erk1/2 and AKT or JNK signaling pathways.