Dataset Information

Interplay between ?Np63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.

ABSTRACT: TP63 acts as a master regulator in epithelia development and in the progression of various cancers, but its role in oral cancer pathogenesis remains unknown. This study aimed to explore the role of TP63 in the progression of oral squamous cell carcinoma (OSCC). This study shows that ?Np63, the predominant isoform of TP63, is significantly upregulated in OSCC tissues and cell lines compared with their normal counterparts, and its expression is closely correlated with pathological differentiation, lymph node metastasis and clinical stage in patients with OSCC. The overexpression of ?Np63 promotes growth, metastasis and stem-like properties in OSCC cells, and ?Np63 depletion significantly represses OSCC cellular phenotypes in vitro and in vivo. The ?Np63 isoform transcriptionally suppresses miR-138-5p expression; restoration of miR-138-5p expression partially abolishes the effect of upregulating ?Np63. This study also demonstrates that miR-138-5p directly targets ?Np63, resulting in crosstalk with ?Np63. The correlation between ?Np63 and miR-138-5p was further validated in OSCC tissues and was found to be significantly associated with the prognosis of patients with OSCC. Therefore, our data reveal that the interplay between ?Np63 and miR-138-5p promotes OSCC progression by regulating cell growth, metastasis and stemness.

SUBMITTER: Zhuang Z

PROVIDER: S-EPMC5400637 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.

Zhuang Zehang Z Xie Nan N Hu Jing J Yu Pei P Wang Cheng C Hu Xingxue X Han Xiaozhe X Hou Jinsong J Huang Hongzhang H Liu Xiqiang X

Oncotarget 20170301 13

TP63 acts as a master regulator in epithelia development and in the progression of various cancers, but its role in oral cancer pathogenesis remains unknown. This study aimed to explore the role of TP63 in the progression of oral squamous cell carcinoma (OSCC). This study shows that ΔNp63, the predominant isoform of TP63, is significantly upregulated in OSCC tissues and cell lines compared with their normal counterparts, and its expression is closely correlated with pathological differentiation, ...[more]

PMID: 28423539

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Project description:BACKGROUND:Non small cell lung cancer (NSCLC) is one of the most common cancers in the world. DHA is known to be capable of suppressing NSCLC cell proliferation and metastasis. However, the mechanisms by which DHA exhibits its antitumor effects are unknown. Here we aimed to identify the effects and mechanisms of DHA and its metabolites on lung cancer cell growth and invasion. METHODS:As measures of cell proliferation and invasion ability, the cell viability and transwell assays were used in vitro. Transgenic mfat-1 mice, which convert ?-6 PUFAs to ?-3 PUFAs, were used to detect the effect of endogenous DHA on tumor transplantation. An LC?-?MS/MS analysis identified the elevation of several eicosanoid metabolites of DHA. By using qPCR miRNA microarray, online prediction software, luciferase reporter assays and Western blot analysis, we further elucidated the mechanisms. RESULTS:Addition of exogenous DHA inhibited the growth and invasion in NSCLC cells in vitro. Endogenously produced DHA attenuated LLC-derived tumor growth and metastasis in the transgenic mfat-1 mice. Among the elevation of DHA metabolites, resolvin D1 (RvD1) significantly contributed to the inhibition in cell growth and invasion. MiRNA microarray revealed that the level of miR-138-5p was significantly increased after RvD1 treatment. MiR-138-5p mimics decreased cell viability and invasion; while miR-138-5p inhibitor abolished RvD1-mediated suppression of cell viability and invasion. The expression of FOXC1 was significantly reduced upon overexpression of miR-138-5p while luciferase reporter assay showed that FOXC1 was a direct target of miR-138-5p. In vivo, endogenous DHA by the mfat-1 transgene enhanced miR-138-5p expression and decreased FOXC1 expression. Furthermore, overexpression of FOXC1 reversed the inhibition in cell viability and invasion induced by RvD1 treatment. CONCLUSIONS:These data identified the RvD1/miR-138-5p/FOXC1 pathway as a novel mechanism by DHA and its metabolite, RvD1, and the potential of targeting such pathway as a therapeutic strategy in treating NSCLC.

Dataset Information

Interplay between ?Np63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.

Publications

Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.

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