Nf kappab and cancer how intimate is this relationship right

NF-kappaB and cancer: how intimate is this relationship.

nf kappab and cancer how intimate is this relationship right

Running title: TIGAR regulation of NF-κB signaling Similarly, in some tumor cell models, TIGAR was found to contribute to the anti-tumor .. demonstrated an intimate and co-dependent relationship between metabolism and NF- immunoblottted for Flag-HOIP, HA-NEMO and TIGAR (right panel, lanes. A direct role of the NF-κB pathway in arsenic-induced apoptosis is shown by .. To show a causal relationship between inhibition of NF-κB and arsenic-induced . Right panels: modulation of NF-κB activity in LCy and HD-MyZ tumor cells in .. Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales. Our findings unveil a new role for p53 in the repression of NF-κB by glucocorticoids and . 2B, Right). p53 loss was confirmed in these cells by qPCR (Fig. . Current insight into the relationship between p53 and GR is unclear. . ( ) Rel/NF-κ B/I κ B family: Intimate tales of association and dissociation.

In this study, we suggest that Ser is a more predominant phosphorylation site on YBX1 than Ser However, details are still unknown regarding the exact order of these phosphorylation events. Furthermore, the IF data Fig. The concept of protein modulators of RelA, i. In their report, the authors provided a repertoire of near modulators for experimental validation.

Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches

Remarkably, one of their predicted novel modulators was YBX1. Therefore, this study is of great novelty and significance. In a broader scope, a fascinating aspect regarding the novel phosphorylation of Ser and Ser of YBX1 could be its potential influence on the overall YBX1 functions. For instance, YBX1 is well known for playing an important role in translation control. In the future, it would be of immense interest to explore whether phosphorylation of Ser and Ser on YBX1 may play any role in translational control of EMT genes as well as other important functions of YBX1.

Finally, this research may provide a potential therapeutic approach in colon cancer treatment. In the future, it would be very interesting to explore whether phosphorylation of Ser and Ser of YBX1 could be generalized to some other types of cancer beyond colon cancer, therefore providing novel therapeutic approaches to other types of cancer as well.

Experimental Procedures Cell Lines and Antibodies The cell line has been described previously The following antibodies were obtained from commercial sources: The mutated site was then confirmed by sequencing.

Expression of the respective constructs was confirmed using Western blotting with specific antibodies. The same numbers of these cells under the same conditions were then infected with the same titers of viruses for either WT-YBX1 or the SA mutant.

Cells were then selected under either 0.

Novel Serine Phosphorylation of YBX1 Activates NF-κB in Colon Cancer

Two stable pools per cell line were collected. Transfections and luciferase assays were carried out as described previously Different antibodies were used based on different experiments as described in the text. Whole cell lysates were prepared and analyzed as described previously 1. Cells were seeded in triplicate and counted on different days using a cell counting chamber. Cell culture dishes were coated with 1. Cells were resuspended in 0.

Cells were cultured for 2—3 weeks before being checked under a microscope, measured, and quantified with the aid of ImageJ software http: The gel was destained with distilled water for 2 h before analysis by MS. Forty-eight hours later, the cells were harvested, and the luciferase activity was measured using a Dual-Luciferase Reporter Assay kit Promega Corp.

Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches

All statistical analyses were performed using SPSS The Kaplan-Meier method and the log-rank test were performed to analyze the prognostic significance. NIK is a direct target of miRa-3p To determine the functional significance of the downregulation of miRa-3p, we attempted to identify the target genes of miRa-3p using computational algorithms.

nf kappab and cancer how intimate is this relationship right

To experimentally identify the target genes of miRa-3p, we performed reporter-based screens as described below. As shown in Fig.

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To identify the regulatory sequence in the 3' UTR of NIK, we constructed additional reporters with mutated sequences in the seed region Fig. The reporter containing the mutated miRa-3p seed sequence prevented the effects of anti-miRa-3p treatment Fig. B Reporter-based miRa-3p target gene screening. The red box represents the mutated target region.

To assess the biological function of miRa-3p in apoptotic signals, we transfected miRa-3p mimics into the LoVo cells, and found that trans-fection with miRa-3p mimics promoted the apoptosis of the LoVo cells Fig.

In addition, miRa-3p overexpression led to the activation of caspase-3 Fig.

nf kappab and cancer how intimate is this relationship right

Collectively, these findings indicate that miRa-3p mediates apoptosis through the suppression of NIK in colonic cell lines. To demonstrate the role of miRa-3p in cancer cell survival, we examined whether the transfection of miRa-3p mimics resulted in a killing effect against the cancer cells, and the number of apoptotic cells was determined by Hoechst staining.

The results revealed that the expression of miRa-3p facilitated tumor cell death Fig. Taken together, these lines of experimental evidence definitively support two notions: B Transfection with miRa-3p mimics promoted the apoptosis of the LoVo cells.

C Overexpression of miRa-3p led to the activation of caspase Increasing evidence has suggested the important role of miRNAs in cancer progression 22 For instance, miR, miR and miR have been shown to increase the resistance of CRC cells to 5-fluorouracil 5-FU 24 — 26and a polymorphism in pre-miRa has been shown to significantly correlate with the risk of developing CRC Furthermore, miR is increased in colorectal carcinoma, suggesting that it is a potential prognostic factor for CRC 28 — However, the role of miRa-3p in CRC remaines to be elucidated.

In this study, we mainly focused on the functional significance of miRa-3p in abnormal CRC cell proliferation.

nf kappab and cancer how intimate is this relationship right

Our results revealed a profound downregulation of miRa-3p in all CRC cases, suggesting that the loss of miRa-3p is a prerequisite for the development of CRC. These results indicate that the downregulation of miRa-3p may be a common occurrence in CRC and that miRa-3p may be used as a biomarker to predict clinical outcome and metastasis in patients with CRC. In the present study, we identified NIK as a target of miRa-3p. By combining a specific inhibitor and mutations in the miRa-3p-binding site, we demonstrated that miRa-3p recognizes and negatively regulates the 3' UTR of NIK Fig.

Second, by introducing an miRa-3p precursor or inhibitor, we demonstrated that the amount of miRa-3p inversely correlates with the levels of expression and downstream signaling of NIK. Collectively, we provide definitive evidence demonstrating that miRa-3p negatively regulates NIK expression and activity. These findings suggest that an aberrant gene expression pattern correlates with the malignant phenotype, which provides important clues as to the clinical manifestations and may help identify therapeutic targets in CRC cells.

Moreover, our results provide evidence indicating that miRa-3p is an important tumor suppressor. Acknowledgments This study was funded by the Science and Technology Program. We appreciate the work from all researchers in this article.

CA Cancer J Clin. Tax-independent constitutive IkappaB kinase activation in adult T-cell leukemia cells. How intimate is this relationship.