RETRACTED ARTICLE: A positive feedback loop consisting of C12orf59/NF-κB/CDH11 promotes gastric cancer invasion and metastasis

Abstract

Background Metastasis remains the main cause of cancer-related death for gastric cancer (GC) patients, but the mechanisms are poorly understood. Using The Cancer Genome Atlas (TCGA) data base and bioinformatics analyses, we identified C12orf59 might act as a potential oncogenic protein in GC. Methods We investigate the expression pattern and clinical significance of C12orf59 in two independent cohorts of GC samples. In the training cohort, we used the X-tile program software to generate the optimal cutoff value for C12orf59 expression in order to classify patients accurately according to clinical outcome. In the validation cohort, this derived cutoff score was applied to exam the association of C12orf59 expression with survival outcome. A series of in vivo and in vitro assays were then performed to investigate the function of C12orf59 in GC. Results C12orf59 was significantly upregulated, and associated with poor survival outcome in two cohorts of GC samples. Gain- and loss of- function studies demonstrated C12orf59 promotes GC cell invasive and metastatic capacity both in vitro and in vivo, and induces epithelial–mesenchymal transition and angiogenesis. Mechanically, C12orf59 exerts oncogenic functions by up-regulating CDH11 expression via NF-κB signaling. Interesting, CDH11 could in turn promote NF-κB bind to C12orf59’s promoter and form a positive feedback loop to sustain the metastatic ability of GC cells. Additionally, downregulation of miR-654-5p is another important mechanism for C12orf59 overexpression in GC. Conclusion Our finding suggested the newly identified C12orf59/NF-κB/CDH11 feedback loop may represent a new strategy for GC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-019-1114-2) contains supplementary material, which is available to authorized users.

TMEM52B suppression promotes cancer cell survival and invasion through modulating E-cadherin stability and EGFR activity

“…Consistent with our results, it has been recently reported that the downregulation of TMEM52B correlated with poor survival of renal cell carcinoma patients [ 10 ]. In contrast, TMEM52B is also associated with poor survival of gastric cancer patients, and reported to promote gastric cancer cell invasiveness and metastatic capacity [ 30 ]. Whether TMEM52B exerts positive or negative influences by cancer type or in a context-dependent manner needs to be further explored.…”

Clinical and prognostic association of oncogene cadherin 11 in gastric cancer

“…One of its basic functions is to mediate cell-cell and cell-matrix junctions, thus regulating cell movement and the epithelial-mesenchymal transition (32,33). In addition to its involvement in cell movement, CDH11 is a positive regulator of NF-κB signaling (34). Upregulated CDH11 in GC increases NF-κB activity and promotes the nuclear localization of NF-κB p65, leading to cell invasion and metastasis.…”

Inferences of individual differences in response to tripterysium glycosides across patients with Rheumatoid arthritis using a novel ceRNA regulatory axis

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