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Distant metastasis frequently occurs in oral squamous cell carcinoma (OSCC) and contributes to the adverse prognosis for patients with OSCC. However, the potential mechanisms behind the metastasis have not yet been clarified. This study investigated the role of miR-378 in the migration and invasiveness of OSCC in vitro and in vivo. According to our results, the migration and invasiveness of OSCC cells were increased in cells overexpressing miR-378, and reduced in cells where miR-378-3p/5p was silenced. In addition, overexpression of miR-378 suppressed the expressions and activities of matrix metalloproteinase 9 (MMP-9) and MMP-2. Epithelial--mesenchymal transition (EMT) was restrained by overexpression of miR-378, as evidenced by an increase in E-cadherin expression and decrease in N-cadherin and uPA expression. However, knockdown of miR-378-3p/5p produced the opposite results. Moreover, kallikrein-related peptidase 4 (KLK4) was confirmed to be a target gene of miR-378. Overexpression of KLK4 reversed the induced decrease in migration and invasiveness of cells overexpressing miR-378 by upregulating the levels of MMP-9, MMP-2, and N-cadherin, and downregulating the level of E-cadhrin. Finally, the number of metastasis nodules in the lung tissues of nude mice was reduced by overexpression of miR-378, whereas the number of metastases increased with knockdown of miR-378. Taken together, our results suggest that the miR-378--KLK4 axis is involved in the mechanisms behind the migration and invasiveness of OSCC cells. Targeting the miR-378--KLK4 axis may be an effective measure for treating OSCC. Key words: miR-378, oral squamous cell carcinoma, KLK4, migration, invasiveness. La métastase à distance survient fréquemment dans le carcinome épidermoïde oral (CEO) et elle contribue au mauvais pronostic du CEO. Toutefois, les mécanismes potentiels qui sous-tendent la métastase n'ont pas encore été clarifiés. Cette étude visait à évaluer le rôle du miR-378 dans la migration et l'invasion du CEO in vitro et in vivo. Selon les résultats obtenus par les auteurs, les capacités de migration et d'invasion étaient accrues chez les cellules qui surexprimaient le miR-378, alors qu'elles diminuaient chez les cellules soumises à un silençage du miR-378-3p/5p. De plus, la surexpression du miR-378 supprimait l'expression et l'activité de MMP-9 et MMP-2. La transition épithélio-mésenchymateuse (TEM) était freinée par la surexpression du miR-378 comme le démontrait l'accroissement de l'expression de la E-cadhérine et la diminution de l'expression de la N-cadhérine et de l'urokinase. En outre, le knockdown du miR-378-3p/5p exerçait l'effet inverse. De plus, la peptidase KLK4 (kallikrein-related peptidase 4) s'avérait être le gène cible du miR-378. La surexpression de KLK4 renversait la diminution de la migration et de l'invasion des cellules induites par la surexpression de miR-378, au moyen de la régulation à la hausse des niveaux de MMP-9, MMP-2 et de N-cadhérine et la régulation à la baisse des niveaux de E-cadhérine. Finalement, le nombre de métastases pulmonaires chez les souris nues était réduit par la surexpression du miR-378 alors que le knockdown du miR-378 provoquait une augmentation du nombre de nodules métastatiques. Dans l'ensemble, leur étude suggère que l'axe miR-378-KLK4estimpliqué dans les mécanismesdemigrationetd'invasion des cellulesdeCEO.Leciblagedel'axe miR-378--KLK4 pourrait constituer une mesure efficace de traitement du CEO. [Traduit par la Rédaction] Mots-clés : miR-378, carcinome épidermoïde oral, KLK4, migration, invasion., Oral malignancy is one of the most common kinds of head and neck cancer, and its main pathology type is squamous-cell carcinoma. The overall prognosis for patients with oral squamous [...]

Recent studies, which aim to optimize maxillary sinus augmentation, have paid significant attention exploring osteogenic potential of maxillary Schneiderian sinus membrane-derived cells (MSSM-derived cells). However, it remains unclear that how MSSM-derived cells could respond to niche's biomechanical properties. Herein, this study investigated the possible effects of substrate stiffness on rMSSM-derived stem cell fate. Initially, rMSSM-derived stem cells with multiple differentiation potential were successfully obtained. We then fabricated polyacrylamide substrates with varied stiffness ranging from 13 to 68 kPa to modulate the mechanical environment of rMSSM-derived stem cells. A larger cell spreading area and increased proliferation of rMSSM-derived stem cells were found on the stiffer substrates. Similarly, cells became more adhesive as their stiffness increased. Furthermore, the higher stiffness facilitated osteogenic differentiation of rMSSM-derived stem cells. Overall, our results indicated that increase in stiffness could mediate behaviors of rMSSM-derived stem cells, which may serve as a guide in future research to design novel biomaterials for maxillary sinus augmentation. [ABSTRACT FROM AUTHOR]