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

Abstract

The aim of this study was to explore the functions and associated mechanisms of long noncoding RNA LINC02487 in oral squamous cell carcinoma (OSCC). Methods:The relative expression levels of LINC02487 in OSCC cell lines and tissue samples were examined by RT-qPCR. Intracellular localization was determined using RNA fluorescence in situ hybridization. LINC02487 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. LINC02487-binding proteins were identified by ChIRP-MS and confirmed by RNA immunoprecipitation. Protein expression was determined by western blotting assay.Results: LINC02487 has been reported to be downregulated in OSCC. Here, we confirmed that the expression of LINC02487 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 LINC02487 expression levels were associated with cancer metastasis. We further identified that LINC02487 was localized to the cytoplasm, aggregated around the nuclear membrane. Functional studies demonstrate that overexpression of LINC02487 significantly suppresses cell migration and invasion and also inhibits cell proliferation. For the mechanism, we reveal that LINC02487 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). Conclusion:Our results confirm that long noncoding RNA LINC02487 is downregulated in OSCC tissue samples and cell lines. We also find that LINC02487 acts as a tumor suppressor through the USP17-SNAI1 axis.

Long Intergenic Non-Coding RNAs in HNSCC: From “Junk DNA” to Important Prognostic Factor

“…Long non-protein-coding RNA 2487 (LINC02487) is a molecule mostly localized in the cytoplasm, retained close to the nuclear membrane, where it displays its regulatory function at the post-transcriptional or post-translational level [87]. Recently, it has been proven that this lincRNA is dysregulated in OSCC and its characteristic for oral carcinogenic tissue low expression is correlated with unfavorable clinical outcome and poor survival [88].…”

“…Feng et al determined that LINC02487 expression is correlated with the OSCC development stage and its level increases from the amount characteristic for adjacent normal tissue, through cancer tissue to the highest expression value in samples from patients with metastasis. Part of their study based on cancerous cell cultures resulted in the observation that overexpression of LINC02487 has an inhibiting impact on OSCC proliferation, migration, and invasiveness [87]. Additionally, up-regulation of LINC02487 regulates the levels of EMT markers and causes a decrease in N-cadherin and vimentin, along with an increase in E-cadherin, through interaction with ubiquitin carboxyl-terminal hydrolase 17 (USP17), a known EMT regulator [89].…”

“…Additionally, up-regulation of LINC02487 regulates the levels of EMT markers and causes a decrease in N-cadherin and vimentin, along with an increase in E-cadherin, through interaction with ubiquitin carboxyl-terminal hydrolase 17 (USP17), a known EMT regulator [89]. Significant differences between tumor tissue and healthy oral mucosa, taken together with its proven OSCC suppressor role [86,87], indicate that LINC02487 can become a unique diagnostic and prognostic biomarker that could lower the high mortality rate caused by distant metastasis [88,90].…”

OUP accepted manuscript

“…Lu Feng et al. found LINC02487 was downregulated in neck squamous cell carcinoma ( 105 ). Yuxing Zhu et al.…”

Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance of Head and Neck Cancer: From Basic Research to Clinical Application

“…Many previous studies have reported the dysregulation and function of ncRNAs in HNC ( Wang et al, 2018 ; Jiang et al, 2019 ; Vo et al, 2019 ). NcRNAs could regulate the expression of genes associated with cell cycle, cell apoptosis, invasion, and migration, and eventually affect the proliferation, invasion, and metastasis of HNC ( Feng et al, 2020 ; Gu et al, 2020 ; Huang et al, 2020 ; Sur et al, 2020 ; Wang et al, 2020 ; Zhang et al, 2020 ). Additionally, researchers reported that several ncRNAs were also dysregulated in radiotherapy-sensitive or radiotherapy-resistant HNC tissues compared with the normal cancer tissues ( Zhang et al, 2013 ; de Jong et al, 2015 ; Qu et al, 2015a , b ; Suh et al, 2015 ; Xu et al, 2015 ; Gao et al, 2017a ; Hess et al, 2017 ; Chen et al, 2019 ; Vahabi et al, 2019 ; Pasi et al, 2020 ).…”