Background: Increased protein N-glycosylation and aberrant Wnt signaling are features of oral cancer. Results: Overexpression of pro-migratory protein CTHRC1 is due to hyperglycosylation and transcriptional activation by canonical Wnt. Conclusion: N-Glycosylation collaborates with canonical Wnt to induce CTHRC1 and drive OSCC cell migration. Significance: Elucidating how N-glycosylation impacts tumor-promoting proteins is critical to understand cancer development and progression.

The tumorigenesis and metastasis of tumors are associated with human collagen triple helix repeats containing 1 (CTHRC1). To study the effects and possible impacting mechanisms of CTHRC1 on human cervical carcinoma development, samples of paraffin-embedded cervical carcinoma and HeLa cells were examined. Immunofluorescence, cell wound scratch assay, western blot analysis and Transwell invasion assay were used to evaluate HeLa cells in response to silencing of the CTHRC1 gene in cervical carcinoma. The expression levels of gap-associated proteins of the Wnt/PCP pathway in paraffin-embedded cervical carcinoma samples were also evaluated by immunohistochemical staining. CTHRC1 promoted the migration and invasion of HeLa cells in vitro, downregulated Ror2 and p-c-Jun and activated the Wnt/PCP pathway. Furthermore, the expression of p-c-Jun, Ror2 and Wnt5a was increased after overexpression of CTHRC1 as revealed in HeLa cells compared to control group. The present experiments revealed that CTHRC1 promoted HeLa cell progression by activating the Wnt/PCP signaling pathway and may play a key role in the invasion and metastasis of cervical carcinoma.

This study is aimed to explore the regulatory effect of lncRNA HOTAIR/miR‐148a/DLGAP1 axis on head and neck tumor (HNT) cell growth, cell mobility, and invasiveness. HOTAIRM1, miR‐148a, and DLGAP1 level in HNT tissues and adjacent normal tissues were measured by qRT‐PCR. Cell Counting Kit‐8 (CCK‐8) and Transwell (migration and invasion) assay were used to survey the influence of HOTAIRM1, miR‐148a, and DLGAP1 on Fadu cells. Nude mouse xenograft was utilized to validate the influence of HOTAIRM1 in vivo. Dual‐luciferase reporter assay confirms the relationship between HOTAIRM1 and miR‐148a, miR‐148a, and DLGAP1. The expression level of HOTAIRM1 was downregulated in human HNT tissues and cells. Overexpression of HOTAIRM1 significantly moderated Fadu cells proliferation, apoptosis, migration, and invasion in vitro and impaired the tumorigenesis in vivo. The expression level of miR‐148a was upregulated in human HNT tissue compared to the adjacent tissues. We identified that miR‐148a was a target of HOTAIRM1 and its expression levels were reduced by HOTAIRM1. Transfection of miR‐148a mimics increased proliferation, migration, and invasion of Fadu cells. DLGAP1 was identified as a novel target of miR‐148a and its expression level was promoted by either HOTAIRM1 overexpression or miR‐148a knockdown. Overexpression of DLGAP1 also facilitated the cell viability and metastasis of Fadu cells. HOTAIRM1 was confirmed as a tumor suppressor via sponging miR‐148a and promote the expression of DLGAP1, which could be regarded as an important target for the prevention and treatment of HNT.

To investigate the effects and the possible underlying mechanisms of nicotine stimulation on tongue squamous cell carcinoma (TSCC) progression, a TSCC cell line Cal27 and 34 samples of paraffin-embedded TSCC were examined. Immunofluorescence, western blot analysis, and TOP/FOP flash, CCK-8, wound healing and Transwell invasion assays were used to evaluate Cal27 in response to nicotine stimulation. We also investigated expression levels of related proteins of Wnt/β-catenin and Wnt/PCP pathways in paraffin-embedded TSCC samples with or without a history of smoking by immunohistochemistry. Nicotine stimulation can promote proliferation, migration, and invasion of TSCC cells in vitro, downregulate E-cadherin, and activate the Wnt/β-catenin and Wnt/PCP pathways, which could be antagonized by the α7 nicotine acetylcholine receptor (α7 nAChR) inhibitor α-BTX. Moreover, the expression levels of β-catenin, Wnt5a and Ror2 were higher in TSCC patients with a history of smoking than those without a history of smoking. Our results suggest nicotine may promote tongue squamous carcinoma cells progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways and may play a significant role in the progression and metastasis of smoking-related TSCC.

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