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Alterations in expression profile of iron-related genes in colorectal cancer.

Hamara K, Bielecka-Kowalska A, Przybylowska-Sygut K, Sygut A, Dziki A, Szemraj J - Mol. Biol. Rep. (2013)

Bottom Line: For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC.We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage.These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

View Article: PubMed Central - PubMed

ABSTRACT
Iron can play a role in colorectal cancer (CRC) development. The expression of genes involved in iron metabolism and its regulation in CRC has not been investigated well. Also the correlation between the level of iron-related genes expression and cancer progression is not known. In this study we collected paired samples of primary adenocarcinoma and adjacent normal mucosa from 73 patients. We assessed the mRNA or miRNA levels of 21 genes and verify their association with clinicopathological characteristics of CRC patients. Our experiments revealed, that the level of divalent metal transporter 1 transcript is well correlated with mRNA levels of iron regulatory proteins (IRPs) in tumor specimens. We have shown, that IRP2 can also be engaged in the mRNA stabilization of other iron transporter-transferrin receptor 1 (TfR1) in early stage of disease, however, in more advanced stages of CRC, mRNA level of TfR1 is related to miR-31 level. For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC. We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage. These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

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Correlation between miR-194 level and a FPN1 mRNA or b ferroportin levels in patients with IIIA and B stages of CRC. Data presented as relative expression of analyzed genes calculated as  or relative amount of protein calculated as ln tumor/nontumor concentration ratio. Correlation coefficients and statistical significance were estimated with Pearson’s correlation coefficient analyses and were r = −0.89, p < 0.001 for FPN1 mRNA vs. miR-194, r = −0.66, p = 0.002 for miR-194 versus ferroportin, n = 20. Dashed lines determine 95 % confidence interval
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Fig5: Correlation between miR-194 level and a FPN1 mRNA or b ferroportin levels in patients with IIIA and B stages of CRC. Data presented as relative expression of analyzed genes calculated as or relative amount of protein calculated as ln tumor/nontumor concentration ratio. Correlation coefficients and statistical significance were estimated with Pearson’s correlation coefficient analyses and were r = −0.89, p < 0.001 for FPN1 mRNA vs. miR-194, r = −0.66, p = 0.002 for miR-194 versus ferroportin, n = 20. Dashed lines determine 95 % confidence interval

Mentions: To further investigate, whether those correlations can be confirmed at the protein level, we estimated the concentration of ferritin and ferroportin in tumor and normal specimens. Strong negative correlation (r = −0.66, p = 0.002) in IIIA and IIIB stages of CRC was observed between FPN1 and miR-194 levels (Fig. 5), but not with FPN1 and IRP1 mRNA levels. However, concentration of this transporter was not associated with its regulatory molecules in early stages of this disease. Similarly to FPN1, the level of other analyzed protein Fn was negatively associated with IRP1 mRNA level but positively correlated with miR-133a level (r = −0.97, p < 0.001 and r = 0.56, p = 0.011, respectively) in patients having lymph nodes invaded by the tumor, which was shown in Fig. 6.Fig. 5


Alterations in expression profile of iron-related genes in colorectal cancer.

Hamara K, Bielecka-Kowalska A, Przybylowska-Sygut K, Sygut A, Dziki A, Szemraj J - Mol. Biol. Rep. (2013)

Correlation between miR-194 level and a FPN1 mRNA or b ferroportin levels in patients with IIIA and B stages of CRC. Data presented as relative expression of analyzed genes calculated as  or relative amount of protein calculated as ln tumor/nontumor concentration ratio. Correlation coefficients and statistical significance were estimated with Pearson’s correlation coefficient analyses and were r = −0.89, p < 0.001 for FPN1 mRNA vs. miR-194, r = −0.66, p = 0.002 for miR-194 versus ferroportin, n = 20. Dashed lines determine 95 % confidence interval
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824343&req=5

Fig5: Correlation between miR-194 level and a FPN1 mRNA or b ferroportin levels in patients with IIIA and B stages of CRC. Data presented as relative expression of analyzed genes calculated as or relative amount of protein calculated as ln tumor/nontumor concentration ratio. Correlation coefficients and statistical significance were estimated with Pearson’s correlation coefficient analyses and were r = −0.89, p < 0.001 for FPN1 mRNA vs. miR-194, r = −0.66, p = 0.002 for miR-194 versus ferroportin, n = 20. Dashed lines determine 95 % confidence interval
Mentions: To further investigate, whether those correlations can be confirmed at the protein level, we estimated the concentration of ferritin and ferroportin in tumor and normal specimens. Strong negative correlation (r = −0.66, p = 0.002) in IIIA and IIIB stages of CRC was observed between FPN1 and miR-194 levels (Fig. 5), but not with FPN1 and IRP1 mRNA levels. However, concentration of this transporter was not associated with its regulatory molecules in early stages of this disease. Similarly to FPN1, the level of other analyzed protein Fn was negatively associated with IRP1 mRNA level but positively correlated with miR-133a level (r = −0.97, p < 0.001 and r = 0.56, p = 0.011, respectively) in patients having lymph nodes invaded by the tumor, which was shown in Fig. 6.Fig. 5

Bottom Line: For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC.We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage.These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

View Article: PubMed Central - PubMed

ABSTRACT
Iron can play a role in colorectal cancer (CRC) development. The expression of genes involved in iron metabolism and its regulation in CRC has not been investigated well. Also the correlation between the level of iron-related genes expression and cancer progression is not known. In this study we collected paired samples of primary adenocarcinoma and adjacent normal mucosa from 73 patients. We assessed the mRNA or miRNA levels of 21 genes and verify their association with clinicopathological characteristics of CRC patients. Our experiments revealed, that the level of divalent metal transporter 1 transcript is well correlated with mRNA levels of iron regulatory proteins (IRPs) in tumor specimens. We have shown, that IRP2 can also be engaged in the mRNA stabilization of other iron transporter-transferrin receptor 1 (TfR1) in early stage of disease, however, in more advanced stages of CRC, mRNA level of TfR1 is related to miR-31 level. For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC. We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage. These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

Show MeSH
Related in: MedlinePlus