AUTHOR=Feng Lu , Zhang Jianjun , Sun Minglei , Qiu Feng , Chen Wantao , Qiu Weiliu 

TITLE=Tumor Suppressor LINC02487 Inhibits Oral Squamous Cell Carcinoma Cell Migration and Invasion Through the USP17–SNAI1 Axis

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.559808

DOI=10.3389/fonc.2020.559808

ISSN=2234-943X

ABSTRACT=<sec><title>Purpose</title><p>The aim of this study was to explore the functions and associated mechanisms of long noncoding RNA <italic>LINC02487</italic> in oral squamous cell carcinoma (OSCC).</p></sec><sec><title>Methods</title><p>The relative expression levels of <italic>LINC02487</italic> in OSCC cell lines and tissue samples were examined by RT-qPCR. Intracellular localization was determined using RNA fluorescence <italic>in situ</italic> hybridization. <italic>LINC02487</italic> was cloned into the pCMV-puro vector and then introduced into OSCC cells using lentiviral transfection. Cell processes, such as proliferation, apoptosis, migration, and invasion, were subsequently examined. <italic>LINC02487</italic>-binding proteins were identified by ChIRP–MS and confirmed by RNA immunoprecipitation. Protein expression was determined by western blotting assay.</p></sec><sec><title>Results</title><p><italic>LINC02487</italic> has been reported to be downregulated in OSCC. Here, we confirmed that the expression of <italic>LINC02487</italic> was reduced in 6 OSCC cell lines compared with that in immortalized normal oral epithelial cells and in 50 OSCC samples compared with paired adjacent normal tissue in a Chinese population and that <italic>LINC02487</italic> expression levels were associated with cancer metastasis. We further identified that <italic>LINC02487</italic> was localized to the cytoplasm, aggregated around the nuclear membrane. Functional studies demonstrate that overexpression of <italic>LINC02487</italic> significantly suppresses cell migration and invasion and also inhibits cell proliferation. For the mechanism, we reveal that <italic>LINC02487</italic> directly binds to USP17, a deubiquitinating enzyme, and regulates cell migration and invasion through the USP17–SNAI1 axis in a process that involves epithelial–mesenchymal transition (EMT).</p></sec><sec><title>Conclusion</title><p>Our results confirm that long noncoding RNA <italic>LINC02487</italic> is downregulated in OSCC tissue samples and cell lines. We also find that <italic>LINC02487</italic> acts as a tumor suppressor through the USP17–SNAI1 axis.</p></sec>