LncRNA, TUG1 regulates the oral squamous cell carcinoma progression possibly via interacting with Wnt/β-catenin signaling.

Oral squamous cell carcinoma (OSCC) is one the most common cancer affecting the head and neck region, and the molecular mechanisms underlying OSCC development is largely unknown. Long non-coding RNAs (lncRNAs) are emerging as key regulators in tumor development. The present study aimed to investigate the role of lncRNA, taurine upregulated gene 1 (TUG1) in OSCC development. The mRNA and protein expression levels were determined by qRT-PCR and western blotting; flow cytometry and ELISA experiments were employed to examine the cell apoptosis; CCK-8 assay, MTT assay, colony formation assay, and cell invasion assay was used to determine cell growth, cell proliferation and cell invasion, respectively. qRT-PCR results showed that TUG1 was up-regulated in both OSCC tissues and cell lines. The high expression level of TUG1 was significantly correlated with TNM stage, lymph node metastasis and tumor grade in OSCC patients. CCK-8 assay, MTT assay, colony formation assay, and cell invasion assay results showed that knock-down of TUG1 by siRNA transfection suppressed cell growth, cell proliferation, and cell invasion in OSCC cell lines (Tca8113 and TSCCA). The cell apoptosis was induced in Tca8113 and TSCCA cells transfected with TUG1 siRNA. In addition, knock-down of TUG1 in Tca8113 and TSCCA cells significantly suppressed the mRNA and protein expression levels of β-catenin, cyclin D1, and c-myc. Wnt/β-catenin pathway activator (LiCl) reversed the TUG1 knock-down effect on cell proliferation, cell invasion and cell apoptosis in Tca8113 and TSCCA cells. In summary, knock-down of TUG1 suppressed cell growth, proliferation and invasion, and also induced apoptosis of OSCC possibly via targeting Wnt/β-catenin signaling. Our data suggest that knock-down of TUG1 may represent a novel therapeutic target for the management of OSCC.

Liang S ，Zhang S ，Wang P ，Yang C ，Shang C ，Yang J ，Wang J ... -  《-》

Long non-coding RNA CCAT1 is a prognostic biomarker for the progression of oral squamous cell carcinoma via miR-181a-mediated Wnt/β-catenin signaling pathway.

Li GH ，Ma ZH ，Wang X 《-》

LncRNA AC007271.3 promotes cell proliferation, invasion, migration and inhibits cell apoptosis of OSCC via the Wnt/β-catenin signaling pathway.

Long noncoding RNA (lncRNA) AC007271.3 has been identified to be dysregulated in oral squamous cell carcinoma (OSCC) in our previous study. However, the precise role of AC007271.3 in OSCC remains unclear. In this study, we investigated the potential functions and the underlying mechanisms of AC007271.3 in OSCC. The expression levels of AC007271.3 in OSCC tissues and cell lines were examined using RT-qPCR. The relationship between AC007271.3 level and clinicopathological characteristics was analyzed, and its association with patient prognosis was assessed by the Kaplan-Meier method. The biological function of AC007271.3 and its role in the development of OSCC through Wnt/β-catenin signaling pathway were studied. We identified that AC007271.3 was up-regulated and positively correlated with advanced clinical stage, lymph node metastasis, poor histological differentiation and unfavorable prognosis. We explored the expression, function, and molecular mechanism of AC007271.3 in OSCC cells. Overexpression of AC007271.3 remarkably promoted cell proliferation in vitro and in vivo, induced cell migration, invasion and inhibited apoptosis in vitro, while knockdown of AC007271.3 attenuated cell proliferation, migration, invasion and induced apoptosis. Mechanistically, AC007271.3 overexpression substantially increased the expression of β-catenin and the downstream target molecules CyclinD1, c-myc and Bcl-2, while silencing of AC007271.3 has the opposite effect. Rescued experiments showed that the ability to promote cell proliferation, migration, invasion and inhibiting apoptosis could be reversed when treated with the Wnt/β-catenin pathway inhibitor. Our data indicated that AC007271.3 could promote cell proliferation, invasion and inhibit cell apoptosis of OSCC via the Wnt/β-catenin signaling pathway, which might provide a novel therapeutic approach for OSCC.

Shao TR ，Zheng ZN ，Chen YC ，Wu QQ ，Huang GZ ，Li F ，Zeng WS ，Lv XZ ... -  《-》

LncRNA MINCR activates Wnt/β-catenin signals to promote cell proliferation and migration in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a common type of malignant oral cancer with high recurrence. MYC-induced long non-coding RNA (MINCR) has been reported as a tumor suppressor in liver cancer and lung cancer. Whereas, it is unknown whether MINCR exerted function in OSCC progression. This study focused on its function and mechanism in OSCC. At first, the expression level of MINCR in OSCC tissues and cell lines as well as corresponding normal controls was evaluated by qRT-PCR assay. The relative high level of MINCR was observed in OSCC tissues and cell lines. The overall survival rate of OSCC patients with high or low level of MINCR was analyzed by using Kaplan-Meier method. In addition, functional assay revealed that MINCR knockdown significantly suppressed OSCC cell proliferation and invasion. Importantly, the effect of MINCR knockdown on Wnt/β-catenin signaling pathway was detected by luciferase reporter and western blot assays. It was found that MINCR knockdown obviously decreased the activity of Wnt/β-catenin pathway. Rescue assays were further used to validate the role of Wnt/β-catenin pathway in MINCR-mediated OSCC progression. The effects of MINCR knockdown on OSCC cell proliferation and migration were partly reversed by the activator of Wnt/β-catenin pathway (LiCl). Overall, our findings revealed that MINCR may be an oncogene in OSCC via modulation of Wnt/β-catenin pathway.

Lyu Q ，Jin L ，Yang X ，Zhang F ... -  《-》

Long non-coding RNA UCA1 contributes to the progression of oral squamous cell carcinoma by regulating the WNT/β-catenin signaling pathway.

With the development of functional genomics studies, a mass of long non-coding RNAs (LncRNA) were discovered from the human genome. Long non-coding RNAs serve as pivotal regulators of genes that are able to generate LncRNA-binding protein complexes to modulate a great number of genes. Recently, the LncRNA urothelial carcinoma-associated 1 (UCA1) has been revealed to be dysregulated, which plays a critical role in the development of a few cancers. However, the role of the biology and clinical significance of UCA1 in the tumorigenesis of oral squamous cell carcinoma (OSCC) remain unknown. We found that UCA1 expression levels were upregulated aberrantly in tongue squamous cell carcinoma tissues and associated with lymph node metastasis and TNM stage. We explored the expression, function, and molecular mechanism of LncRNA UCA1 in OSCC. In the present work, we revealed that UCA1 silencing suppressed proliferation and metastasis and induced apoptosis of OSCC cell lines in vitro and in vivo, which might be related to the activation level of the WNT/β-catenin signaling pathway. Our research results emphasize the pivotal role of UCA1 in the oncogenesis of OSCC and reveal a novel LncRNA UCA1-β-catenin-WNT signaling pathway regulatory network that could contribute to our understanding in the pathogenesis of OSCC and assist in the discovery of a viable LncRNA-directed diagnostic and therapeutic strategy for this fatal disease.

Yang YT ，Wang YF ，Lai JY ，Shen SY ，Wang F ，Kong J ，Zhang W ，Yang HY ... -  《-》