Tongue Squamous Cell Carcinoma Migration Research Articles

IncRNA XIST Targets miR-124/JAG1 via CeRNA Mechanism to Facilitate the Migration and Proliferation of Tongue Squamous Cell Carcinoma.

This study was designed to characterize the effect of lncRNA XIST on the migration as well as proliferation of tongue squamous cell carcinoma (TSCC) and its associated molecular mechanisms. Chip-seq analysis screened the aberrant lncRNA in TSCC patients. CCK-8 and scratch experiment detected cell migration and proliferation in TSCC after lncRNA XIST inhibition. We predicted and verified lncRNA XIST target miRNA. CCK-8 and scratch test examined the cell migration and proliferation effects in TSCC after transfection of miR-124 mimics. Luciferase reporter experiment confirmed the interaction of miR-124 with JAG1. Western blot validated influence of lncRNA XIST on miR-124/JAG1 axis. We found that lncRNA XIST was up-regulated in TSCC patients, and it facilitated the TSCC cell migration and proliferation in vitro. lncRNA XIST regulated miR-124 expression through ceRNA mechanism. Up-regulating miR-124 significantly inhibited TSCC cell migration and proliferation. JAG1 acted as immediate target of miR-124. Moreover, lncRNA XIST targeted miR-124 to regulate JAG1 levels through the ceRNA mechanism. IncRNA XIST encourages TSCC migration and proliferation by modulating miR-124/JAG1 axis.

LncRNA GACAT1 induces tongue squamous cell carcinoma migration and proliferation via miR-149.

Recent studies have observed that lncRNAs (long non‐coding RNAs) are involved in the progression of various tumours including tongue squamous cell carcinoma (TSCC). Recently, a new lnRNA, GACAT1, has been firstly identified in gastric cancer. However, its potential role in TSCC remains unknown. In this reference, we observed that GACAT1 was overexpressed in TSCC samples and cell lines. Of 25 TSCC specimens, GACAT1 expression was overexpressed in 18 patients (18/25, 72%) compared to non‐tumour specimens. Ectopic expression of GACAT1 induced cell growth and migration and promoted epithelial to mesenchymal transition in TSCC. In addition, ectopic expression of GACAT1 decreased miR‐149 expression in SCC1 cell. We observed that miR‐149 expression was down‐regulated in TSCC cell lines. Moreover, we observed that GACAT1 expression was negatively correlated with miR‐149 expression. GACAT1 overexpression induced TSCC cell growth and migration via regulating miR‐149 expression. These data provided that GACAT1 played an oncogenic role in the progression of TSCC partly through modulating miR‐149 expression.

MiRNA-200a Regulating Proliferation, Migration, and Infiltration of Tongue Squamous Cell Carcinoma Cells by Targeting DEK Proto-Oncogene

Tongue squamous cell carcinoma (TSCC) is the most frequently occurring oral cancer and is characterized by high proliferation and metastasis rates. Incomplete understanding of the pathogenesis of TSCC coupled with frequent tongue movement increases the difficulty of therapy. Additionally, TSCC is prone to recurrence and metastasis after treatment. Thus, exploring mechanisms of proliferation, migration, and infiltration of TSCC cancer cells is essential for reducing morbidity and mortality. Transfection of miRNA-200a mimics into SCC15 cells showed that miRNA-200a expression decreased significantly, and DEK expression significantly increased. Transfection of miRNA-200a mimics (miRNA-200a group), negative control mimics (miRNA-NC group), empty vector (miRNA-200a + pcDNA3.1 group), and miRNA-200a mimics and DEK overexpression vector (miRNA-200a + DEK group) into SCC15 cells respectively indicates that overexpression of miRNA-200a substantially inhibits SCC15 cell proliferation, infiltration and migration, decreases PCNA and Vimentin expression, and promotes E-cadherin expression. miRNA-200a + DEK transfection induced greater cell proliferation, infiltration and migration, much higher PCNA and Vimentin expression, and significantly lower E-cadherin expression. Luciferase reporter gene detection of overexpressed DEK or DEK expression after inhibiting miRNA-200a expression indicated a targeting association between miRNA-200a and DEK. miRNA-200a inhibits proliferation, infiltration and migration ability of TSCC by targeting DEK and may represent a novel means for clinical intervention in TSCC. miRNA-200a inhibits proliferation, invasion, and migration of TSCC by targeting DEK.

KLF7 is associated with poor prognosis and regulates migration and adhesion in tongue cancer.

The present study was performed to determine the clinical relevance of KLF7 in tongue squamous cell carcinoma (TSCC) and to characterize its potential function and mechanism of action. KLF7 expression was measured by RT-qPCR in 21 tongue cancer samples. The clinical relevance of KLF7 was analyzed in another cohort of 127 TSCC samples from a public database. Then, we performed RNA sequencing analysis in KLF7-overexpressing TSCC (SCC9 and CAL27) cells to define significantly altered pathways. The possible changes in migration and adhesion were then analyzed in KLF7-overexpressing and knockdown TSCC cells. Our results showed that KLF7 mRNA expression was upregulated in TSCC and was significantly associated with the T and N stages. Patients with high-KLF7 expression had worse overall survival. RNA sequencing and KEGG enriched pathway analysis showed that altered genes were enriched in extracellular matrix-receptor interactions and focal adhesions in both cell lines. KLF7-overexpressing TSCC cell lines showed enhanced migration capacity and cell adhesion ability, and knockdown of KLF7 expression decreased TSCC migration and adhesion ability. We concluded that KLF7 was overexpressed in TSCC and has prognostic value. KLF7 promoted TSCC migration and increased cell adhesion.

H19 Facilitates Tongue Squamous Cell Carcinoma Migration and Invasion via Sponging miR-let-7

The long noncoding RNA (lncRNA) H19 has been described to participate in the metastasis of various tumors. Nevertheless, whether H19 promotes or impedes tongue squamous cell carcinoma (TSCC) cell migration and invasion remains controversial. Here we found that the expression of H19 was elevated in TSCC tissues compared with adjacent normal tissues. Moreover, we demonstrated that the expression of H19 was higher in metastasized tumors compared with unmetastasized tumors. Consistently, TSCC cells express higher levels of H19 than human squamous cells. Subsequently, depletion of H19 impaired the migration and invasion abilities of TSCC cells. Mechanistically, we demonstrated that H19 functions as a competing endogenous RNA (ceRNA) to sponge miRNA let-7a, leading to an increase in a let-7a target, the key regulator of tumor metastasis HMGA2, which is enriched in TSCC tissues and cell lines. Intriguingly, inhibition of let-7a significantly rescued the short hairpin H19 (shH19)-induced decrease in TSCC migration and invasion. These findings revealed that the H19/let-7a/HMGA2/EMT axis plays a critical role in the regulation of TSCC migration and invasion, which may provide a new therapeutic target for TSCC.

Odd-skipped related transcription factor 1 (OSR1) suppresses tongue squamous cell carcinoma migration and invasion through inhibiting NF-κB pathway

Tongue squamous cell carcinoma (TSCC) is the most common cancers of oral, owing to the high invasive and metastatic ability, patients with TSCC have poor prognosis, it's important to explore the regulatory mechanism of TSCC invasion and metastasis. Previous studies suggest OSR1 suppresses the progression of gastric cancer and renal cell carcinoma, but its role in TSCC hasn’t been studied. Here, we found OSR1 was downregulated in TSCC cells and specimens, Transwell and 3D spheroid invasion assay suggested OSR1 overexpression inhibited TSCC cell migration and invasion, while its knockdown promoted TSCC cell migration and invasion. Mechanism analysis found OSR1 expression was negatively correlated with NF-κB pathway and its targets. Western blot and NF-κB activity analysis suggested OSR1 inhibited NF-κB activity. Double inhibition of OSR1 and NF-κB significantly inhibited TSCC cell migration and invasion. These findings suggested OSR1 inhibited TSCC cell migration and invasion through inhibiting NF-κB pathway.

Investigation of proliferation and migration of tongue squamous cell carcinoma promoted by three chemokines, MIP-3α, MIP-1β, and IP-10.

The aim of this work was to investigate the role of chemokines in proliferation and migration of tongue squamous cell carcinoma (TSCC). Out of the 80 cytokines surveyed by a human cytokine antibody array, three chemokines, macrophage inflammatory protein-3α (MIP-3α), macrophage inflammatory protein-1β (MIP-1β), and interferon gamma-induced protein 10 (IP-10), showed elevated expression in TSCC cells (CAL-27 and UM-1), compared to the oral mucosal epithelial cells. Immunohistochemistry confirmed the high level of expression of MIP-3α in the TSCC tissues, especially in the high clinical stages. Furthermore, Western blot and immunofluorescence staining indicated that C-C chemokine receptor type 5, C-C chemokine receptor type 6, and C-X-C motif chemokine receptor 3, which are the receptors for MIP-3α, MIP-1β, and IP-10, respectively, were expressed in the TSCC cells. Viability assay showed MIP-3α, MIP-1β, and IP-10 led to the proliferation of the CAL-27 cells. Interestingly, MIP-1β and IP-10 also induced apoptosis in the TSCC cells. Transwell invasion assay showed MIP-3α and IP-10 could increase the invasive capability of TSCC cells; consistently, the enzymatic activities of matrix metalloproteinase-2 and matrix metalloproteinase-9 increased in the MIP-3α- and IP-10-treated cells. In summary, our results indicate the expression of MIP-3α, MIP-1β, and IP-10 increased in the TSCC cells. The elevated expression of MIP-3α and IP-10 promoted proliferation and migration of TSCC. These chemokines, along with their receptors, could be potential biomarkers and therapeutic targets for TSCC, especially for those in the high clinical stages.

Long non-coding RNA NKILA inhibits migration and invasion of tongue squamous cell carcinoma cells via suppressing epithelial-mesenchymal transition.

Long non-coding RNAs (lncRNAs) have emerged recently as key regulators of tumor development and progression. Our previous study identified an NF-KappaB interacting lncRNA (NKILA) which was negatively correlated with breast cancer metastasis and patient prognosis. However, its clinical significance and potential role in Tongue squamous cell carcinoma (TSCC) remain unclear. Here we show that NKILA is down-regulated in TSCC cancer tissues than that in matched adjacent noncancerous tissues. And low NKILA expression in TSCC is significantly correlated with tumor metastasis and poor patient prognosis. In vitro, overexpression of NKILA decreases TSCC cells migration and invasion. Mechanistic study shows that NKILA inhibits the phosphorylation of IκBα and NF-κB activation as well as the induction of the epithelial-mesenchymal transition (EMT) process. Ectopic expression of NKILA in Tscca cells inhibits NF-κB activator TNF-α-promoted cell migration and invasion, while applying NF-κB inhibitor Bay-117082 or JSH-23 in NKILA silenced CAL27 cells reverses cell migration capacity to lower level. In vivo experimental metastasis model also demonstrates NKILA inhibits lung metastasis of NOD/SCID mice with TSCC tumors. These results suggested that NKILA is a vital determinant of TSCC migration and invasion and NF-κB signaling pathway mediates this effect. Given the above mentioned function of NKILA, it could act as a potential predictor for overall survival in patients with TSCC and a potential therapeutic target for TSCC intervention.