Abstract
Accumulating evidence has indicated that lncRNAs regulate various biological and pathological processes in diverse malignant tumors. The roles of LINC00667 in cancer development have been explored in glioma, hepatocellular carcinoma and non-small cell lung cancer, but not in nasopharyngeal carcinoma (NPC). In the present study, we characterize the role and molecular mechanism of LINC00667 in NPC progression. It was found that LINC00667 was overexpressed in NPC cells compared to normal cells. Silencing LINC00667 suppressed the proliferation, migration, invasion and epithelial mesenchymal transition (EMT) in NPC cells. In addition, bioinformatics analysis revealed that LINC00667 acted as a ceRNA to absorb miR-4319. Further investigations illustrated that miR-4319 had low expression in NPC cells and functioned as a tumor suppressor in the progression of NPC. Mechanistic study identified forkhead box Q1 (FOXQ1) as a functional target of miR-4319. The effect of LINC00667 in NPC development was mediated by the miR-4319/FOXQ1 axis. Analysis on tumorxenograft mouse model demonstrated that knockdown of LINC00667 repressed NPC tumor growth in vivo and confirmed the in vitro results. Our present study suggested that LINC00667 promoted the malignant phenotypes of NPC cells by competitively binding to miR-4319 to up-regulate FOXQ1 expression. Our results reveled that LINC00667 could be a diagnostic and therapeutic target for NPC patients.
Highlights
Nasopharyngeal carcinoma (NPC) is one of the most frequent malignant head and neck tumors, which originate from in the surface epithelium of nasopharynx [1, 2]
We explore the expression of long noncoding RNAs (lncRNAs) LINC00667 in NPC and how it affects the malignant phenotypes of NPC cells
Our results of RNA pull-down assay, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis suggested that the expression of forkhead box Q1 (FOXQ1) was inhibited by miR-4319 mimics or depletion of LINC00667, implicating that LINC00667 might upregulate FOXQ1 by inhibiting miR-4319.our xenograft mouse model validated the role of LINC0066 in promoting NPC cell growth in vivo, and the relationship of LINC0066, miR-4319 and FOXQ1.Our results suggest thatLINC00667 might serve as an oncogene in the development of NPC via targeting miR-4319/ FOXQ1 axis
Summary
Nasopharyngeal carcinoma (NPC) is one of the most frequent malignant head and neck tumors, which originate from in the surface epithelium of nasopharynx [1, 2]. Exploring the pathological mechanism governing NPC tumorigenesis is urgently needed for the treatment of NPC. Dysregulated lncRNAs have been detected in a wide range of pathological states, including human cancers [10, 11]. Accumulating evidence has illustrated that lncRNAs are implicated in the initiation and progression of NPC. Up-regulated lncRNA AFAP1-AS1 expression is associated with NPC progression and poor prognosis [12]. LncRNA LET repressed by EZH2 suppresses NPC cell proliferation and induces apoptosis [13]. The p53-regulated lncRNA LOC401317 restrains cell proliferation and promotes apoptosis in NPC [14].
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