LncRNA HCG18 contributes to nasopharyngeal carcinoma development by modulating miR-140/CCND1 and Hedgehog signaling pathway.

Abstract

Long non-coding RNAs (lncRNAs) exhibit important roles in a variety of biological properties of tumors. LncRNA HCG18 (HCG18) is a newly identified lncRNA whose roles in tumor progression remains largely unclear. The objective of our current research was to explore the roles and the underlying mechanisms of HCG18 in nasopharyngeal carcinoma (NPC). Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to determine the levels of HCG18 in NPC tissue and cell lines. Clinical significances and prognostic values of HCG18 were analyzed using the statistical methods. Cell Counting Kit-8 (CCK-8) assays, clonogenic survival assays, flow cytometry, wound-healing assays, and transwell assays were used to examine the tumorigenesis functions of HCG18 in vitro. Insights of the mechanism of ceRNAs were gained from bioinformatic methods and Luciferase analysis. Western blot was performed to determine the expression of tumor-related pathways. We found that HCG18 expression was upregulated in both NPC specimens and cell lines. Higher levels of HCG18 were associated with positive lymph node metastasis and poor prognosis of NPC patients. Importantly, the multivariate analysis confirmed that HCG18 was an independent risk factor for outcome. Functionally, the downregulation of HCG18 exhibited tumor-suppressive effects via the inhibition of cell proliferation and metastasis. Mechanistically, HCG18 may directly bind to miR-140 and effectively act as a ceRNA for miR-140 to increase the expression of cyclin D1 (CCND1). In addition, HCG18 may contribute to NPC progression via modulating Wnt/β-catenin signaling and Hedgehog pathway. Our findings suggested that HCG18 served as an oncogenic lncRNA in NPC progression, which may provide a novel biomarker of an unfavorable outcome and a potential therapeutic target for NPC.