Given that lymphatic metastasis represents a pivotal determinant of poor clinical outcomes in tongue squamous cell carcinoma (TSCC), this study aimed to elucidate the role of the CXCR4/CXCL12 chemokine axis in TSCC lymphatic metastasis and its clinical significance. We examined CXCR4 and CXCL12 expression in 87 TSCC specimens by immunohistochemistry and analyzed their correlation with clinicopathological features. TSCC cell lines with stable CXCR4 overexpression or knockdown were established to investigate cellular functions through proliferation, migration, invasion, and apoptosis assays. Mechanistic studies were conducted using pharmacological inhibitors, western blotting, and lymphatic endothelial cell functional assays. An orthotopic TSCC mouse model was developed to validate findings in vivo. RNA sequencing was performed to analyze global transcriptomic changes. CXCR4 and CXCL12 were significantly upregulated in TSCC tissues compared to adjacent normal tissues, with expression levels correlating with lymph node metastasis and poor survival. CXCR4 overexpression enhanced TSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition while suppressing apoptosis. Mechanistically, CXCL12 activated the PI3K/AKT pathway in a time- and dose-dependent manner, and pathway inhibition using AMD3100 or LY294002 attenuated pro-metastatic phenotypes. CXCR4/CXCL12 signaling promoted lymphangiogenesis by enhancing lymphatic endothelial cell proliferation, migration, and tube formation. In vivo, CXCR4 overexpression accelerated tumor growth and lymphatic metastasis, while CXCR4 inhibition showed opposite effects. Transcriptomic analysis revealed comprehensive molecular alterations regulated by CXCR4/CXCL12 signaling. The CXCR4/CXCL12 axis functions as a crucial mediator of TSCC lymphatic metastasis by promoting tumor cell invasiveness and lymphangiogenesis via the PI3K/AKT pathway. CXCR4 and CXCL12 serve as independent prognostic biomarkers for TSCC lymphatic metastasis and represent promising therapeutic targets for this aggressive malignancy.

Background. Long noncoding RNA (lncRNA) critically impacts the modulation of tumor developments and progressions. Our study is aimed at investigating the expressing patterns, clinical significance, and biological roles of lncRNA TSPEAR-AS2 (TSPEAR-AS2) in oral squamous cell carcinoma (OSCC). Material and Approach. The expressing states achieved by TSPEAR-AS2 were examined in OSCC specimens and cell lines by RT-PCR. The clinical significance of TSPEAR-AS2 was statistically analyzed. OSCC proliferating, invading, and migrating processes were examined with the use of wound healing assays, transwell, colony formation, and cell counting kit-8. Additionally, the downstream molecular mechanism of TSPEAR-AS2 in OSCC was explored. Results. TSPEAR-AS2 was overexpressed in OSCC tumors and cells. High TSPEAR-AS2 was associated with advanced TNM stage. Patients with high TSPEAR-AS2 expression displayed a shorter disease-free survival and total survival of OSCC patients than those with low TSPEAR-AS2 expressing level. It was found that knockdown of TSPEAR-AS2 could inhibit the proliferating, invading, and migrating processes pertaining to OSCC cells. Luciferase reporter tests and RNA pull-down results revealed that TSPEAR-AS2 enhanced the expressions of PPM1A by regulating miR-487a-3p, and TSPEAR-AS2 could be adopted as a miR-487a-3p sponge to inhibit PPM1A expression. Conclusion. Our study highlighted the significance of the TSPEAR-AS2/miR-487a-3p/PPM1A axis within OSCC progression and offered a novel biomarker and novel strategies for OSCC treatments.

BACKGROUND: For its function of catalysing the reaction of aldehyde to acetic acid, ALDH could be applied to antialcoholismic drug development. However, both of the production and activity of natural ALDH are too low to meet the demand. OBJECTIVE: T