Dataset Information

Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1.

ABSTRACT: Lineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchymal transition, invasion, and metastasis in melanoma cells. We find that these lineage-specific functions of FOXQ1 largely depend on its ability to activate (in carcinomas) or repress (in melanoma) transcription of the N-cadherin gene (CDH2). We demonstrate that FOXQ1 interacts with nuclear ?-catenin and TLE proteins, and the ?-catenin/TLE ratio, which is higher in carcinoma than melanoma cells, determines the effect of FOXQ1 on CDH2 transcription. Accordingly, other FOXQ1-dependent phenotypes can be manipulated by altering nuclear ?-catenin or TLE proteins levels. Our data identify FOXQ1 as a melanoma suppressor and establish a mechanism underlying its inverse lineage-specific transcriptional regulation of transformed phenotypes.

SUBMITTER: Bagati A

PROVIDER: S-EPMC5664207 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1.

Bagati Archis A Bianchi-Smiraglia Anna A Moparthy Sudha S Kolesnikova Kateryna K Fink Emily E EE Lipchick Brittany C BC Kolesnikova Masha M Jowdy Peter P Polechetti Anthony A Mahpour Amin A Ross Jason J Wawrzyniak Joseph A JA Yun Dong Hyun DH Paragh Gyorgy G Kozlova Nadezhda I NI Berman Albert E AE Wang Jianmin J Liu Song S Nemeth Michael J MJ Nikiforov Mikhail A MA

Cell reports 20170901 12

Lineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchymal transition, invasion, and metastasis in melanoma cells. We find that these lineage-specific functions of FOXQ1 largely depend on its ability to activate (in carcinomas) or repress (in melanoma) tr ...[more]

PMID: 28930679

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Project description:BACKGROUND:Circular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown. METHODS:Here, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity. RESULTS:We identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients. CONCLUSIONS:Our findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients.

Dataset Information

Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1.

Publications

Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1.

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