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Filamin C, a dysregulated protein in cancer revealed by label-free quantitative proteomic analyses of human gastric cancer cells.

Qiao J, Cui SJ, Xu LL, Chen SJ, Yao J, Jiang YH, Peng G, Fang CY, Yang PY, Liu F - Oncotarget (2015)

Bottom Line: Nine proteins were significantly dysregulated in all three GC cell lines, including filamin C, a muscle-specific filamin and a large actin-cross-linking protein.Silencing of filamin C increased the expression of matrix metallopeptidase 2 and improved the metastasis of prostate cancer in a zebrafish model.High filamin C associated with better prognosis of prostate cancer, leukemia and breast cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

ABSTRACT
Gastric cancer (GC) is the fourth and fifth most common cancer in men and women, respectively. We identified 2,750 proteins at false discovery rates of 1.3% (protein) and 0.03% (spectrum) by comparing the proteomic profiles of three GC and a normal gastric cell lines. Nine proteins were significantly dysregulated in all three GC cell lines, including filamin C, a muscle-specific filamin and a large actin-cross-linking protein. Downregulation of filamin C in GC cell lines and tissues were verified using quantitative PCR and immunohistochemistry. Data-mining using public microarray datasets shown that filamin C was significantly reduced in many human primary and metastasis cancers. Transient expression or silencing of filamin C affected the proliferation and colony formation of cancer cells. Silencing of endogenous filamin C enhanced cancer cell migration and invasion, whereas ectopic expression of filamin C had opposing effects. Silencing of filamin C increased the expression of matrix metallopeptidase 2 and improved the metastasis of prostate cancer in a zebrafish model. High filamin C associated with better prognosis of prostate cancer, leukemia and breast cancer patients. These findings establish a functional role of filamin C in human cancers and these data will be valuable for further study of its mechanisms.

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Reduced mRNA level of filamin C was commonly detected in various types of human cancers by analyzing the microarray datasets in Oncomine (https://www.oncomine.org/)(A) The filamin C mRNA level was significantly reduced in GC tissues based on the Cui dataset. (B) The filamin C mRNA level was significantly reduced in prostate cancer based on 11 microarray datasets. (C) The filamin C mRNA level was significantly reduced in metastatic tumors of gastric cancer based on the Chen dataset. (D) The filamin C mRNA level was significantly reduced in the lung metastatic tumors of squamous cell carcinomas (Talbot Lung). (E) The filamin C level was significantly reduced in metastatic tumor of prostate cancer compared with the normal tissues and primary prostate cancer tissues based on 8 microarray datasets. The line inside the boxes represents the median value. The box length indicates the interquartile range. The asterisk (*) indicates the extreme value > 3 interquartile ranges from the end of the box. The outliers (o) have values > 1.5 interquartile ranges but < 3 interquartile ranges from the end of the box. The boxplot and error bar width are scaled based on count. N, normal tissues; P, primary cancers; M, metastatic tissues. The numbers under the tissue type indicate the total cases of each cancer type. Statistical significances were calculated using Student's t tests and a p value < 0.05 was considered as statistically significant. The p values separated with slashes indicated the comparisons of normal/primary, normal/metastatic and primary/metastatic cancers.
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Figure 3: Reduced mRNA level of filamin C was commonly detected in various types of human cancers by analyzing the microarray datasets in Oncomine (https://www.oncomine.org/)(A) The filamin C mRNA level was significantly reduced in GC tissues based on the Cui dataset. (B) The filamin C mRNA level was significantly reduced in prostate cancer based on 11 microarray datasets. (C) The filamin C mRNA level was significantly reduced in metastatic tumors of gastric cancer based on the Chen dataset. (D) The filamin C mRNA level was significantly reduced in the lung metastatic tumors of squamous cell carcinomas (Talbot Lung). (E) The filamin C level was significantly reduced in metastatic tumor of prostate cancer compared with the normal tissues and primary prostate cancer tissues based on 8 microarray datasets. The line inside the boxes represents the median value. The box length indicates the interquartile range. The asterisk (*) indicates the extreme value > 3 interquartile ranges from the end of the box. The outliers (o) have values > 1.5 interquartile ranges but < 3 interquartile ranges from the end of the box. The boxplot and error bar width are scaled based on count. N, normal tissues; P, primary cancers; M, metastatic tissues. The numbers under the tissue type indicate the total cases of each cancer type. Statistical significances were calculated using Student's t tests and a p value < 0.05 was considered as statistically significant. The p values separated with slashes indicated the comparisons of normal/primary, normal/metastatic and primary/metastatic cancers.

Mentions: Based on proteomics, qPCR, Western blot, and immunohistochemistry (IHC) analyses, we confirmed that the expression of filamin C was significantly reduced in GC cell lines and tissues compared with that in normal gastric cell line and tissues. Whether downregulation of filamin C is common in other human cancers is not clear. To address this question, we performed a comprehensive analysis of the expression of filamin C in other tumor tissues based on the publically available Oncomine microarray datasets (https://www.oncomine.org/). First, significantly reduced mRNA level of filamin C in GC tissues was identified in the Cui gastric microarray dataset (Figure 3A). Reduced expression of filamin C was also observed in 11 independent datasets of 561 cases of prostate cancer (Figure 3B). In addition, significantly reduced expression of filamin C was detected in 5 datasets of colon cancers (510 cases), 3 datasets of breast cancer (2,564 cases), 3 datasets of bladder cancer (282 cases), 4 datasets of head-neck cancers (95 cases), 1 dataset of leukemia (2,022 cases), 3 datasets of ovarian cancer (674 cases), 1 dataset of esophagus cancer (53 cases), and 4 datasets of lung cancer (410 cases) (Supplementary Figure 3). These observations suggest that filamin C is downregulated in a broad range of human cancers.


Filamin C, a dysregulated protein in cancer revealed by label-free quantitative proteomic analyses of human gastric cancer cells.

Qiao J, Cui SJ, Xu LL, Chen SJ, Yao J, Jiang YH, Peng G, Fang CY, Yang PY, Liu F - Oncotarget (2015)

Reduced mRNA level of filamin C was commonly detected in various types of human cancers by analyzing the microarray datasets in Oncomine (https://www.oncomine.org/)(A) The filamin C mRNA level was significantly reduced in GC tissues based on the Cui dataset. (B) The filamin C mRNA level was significantly reduced in prostate cancer based on 11 microarray datasets. (C) The filamin C mRNA level was significantly reduced in metastatic tumors of gastric cancer based on the Chen dataset. (D) The filamin C mRNA level was significantly reduced in the lung metastatic tumors of squamous cell carcinomas (Talbot Lung). (E) The filamin C level was significantly reduced in metastatic tumor of prostate cancer compared with the normal tissues and primary prostate cancer tissues based on 8 microarray datasets. The line inside the boxes represents the median value. The box length indicates the interquartile range. The asterisk (*) indicates the extreme value > 3 interquartile ranges from the end of the box. The outliers (o) have values > 1.5 interquartile ranges but < 3 interquartile ranges from the end of the box. The boxplot and error bar width are scaled based on count. N, normal tissues; P, primary cancers; M, metastatic tissues. The numbers under the tissue type indicate the total cases of each cancer type. Statistical significances were calculated using Student's t tests and a p value < 0.05 was considered as statistically significant. The p values separated with slashes indicated the comparisons of normal/primary, normal/metastatic and primary/metastatic cancers.
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Related In: Results  -  Collection

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Figure 3: Reduced mRNA level of filamin C was commonly detected in various types of human cancers by analyzing the microarray datasets in Oncomine (https://www.oncomine.org/)(A) The filamin C mRNA level was significantly reduced in GC tissues based on the Cui dataset. (B) The filamin C mRNA level was significantly reduced in prostate cancer based on 11 microarray datasets. (C) The filamin C mRNA level was significantly reduced in metastatic tumors of gastric cancer based on the Chen dataset. (D) The filamin C mRNA level was significantly reduced in the lung metastatic tumors of squamous cell carcinomas (Talbot Lung). (E) The filamin C level was significantly reduced in metastatic tumor of prostate cancer compared with the normal tissues and primary prostate cancer tissues based on 8 microarray datasets. The line inside the boxes represents the median value. The box length indicates the interquartile range. The asterisk (*) indicates the extreme value > 3 interquartile ranges from the end of the box. The outliers (o) have values > 1.5 interquartile ranges but < 3 interquartile ranges from the end of the box. The boxplot and error bar width are scaled based on count. N, normal tissues; P, primary cancers; M, metastatic tissues. The numbers under the tissue type indicate the total cases of each cancer type. Statistical significances were calculated using Student's t tests and a p value < 0.05 was considered as statistically significant. The p values separated with slashes indicated the comparisons of normal/primary, normal/metastatic and primary/metastatic cancers.
Mentions: Based on proteomics, qPCR, Western blot, and immunohistochemistry (IHC) analyses, we confirmed that the expression of filamin C was significantly reduced in GC cell lines and tissues compared with that in normal gastric cell line and tissues. Whether downregulation of filamin C is common in other human cancers is not clear. To address this question, we performed a comprehensive analysis of the expression of filamin C in other tumor tissues based on the publically available Oncomine microarray datasets (https://www.oncomine.org/). First, significantly reduced mRNA level of filamin C in GC tissues was identified in the Cui gastric microarray dataset (Figure 3A). Reduced expression of filamin C was also observed in 11 independent datasets of 561 cases of prostate cancer (Figure 3B). In addition, significantly reduced expression of filamin C was detected in 5 datasets of colon cancers (510 cases), 3 datasets of breast cancer (2,564 cases), 3 datasets of bladder cancer (282 cases), 4 datasets of head-neck cancers (95 cases), 1 dataset of leukemia (2,022 cases), 3 datasets of ovarian cancer (674 cases), 1 dataset of esophagus cancer (53 cases), and 4 datasets of lung cancer (410 cases) (Supplementary Figure 3). These observations suggest that filamin C is downregulated in a broad range of human cancers.

Bottom Line: Nine proteins were significantly dysregulated in all three GC cell lines, including filamin C, a muscle-specific filamin and a large actin-cross-linking protein.Silencing of filamin C increased the expression of matrix metallopeptidase 2 and improved the metastasis of prostate cancer in a zebrafish model.High filamin C associated with better prognosis of prostate cancer, leukemia and breast cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

ABSTRACT
Gastric cancer (GC) is the fourth and fifth most common cancer in men and women, respectively. We identified 2,750 proteins at false discovery rates of 1.3% (protein) and 0.03% (spectrum) by comparing the proteomic profiles of three GC and a normal gastric cell lines. Nine proteins were significantly dysregulated in all three GC cell lines, including filamin C, a muscle-specific filamin and a large actin-cross-linking protein. Downregulation of filamin C in GC cell lines and tissues were verified using quantitative PCR and immunohistochemistry. Data-mining using public microarray datasets shown that filamin C was significantly reduced in many human primary and metastasis cancers. Transient expression or silencing of filamin C affected the proliferation and colony formation of cancer cells. Silencing of endogenous filamin C enhanced cancer cell migration and invasion, whereas ectopic expression of filamin C had opposing effects. Silencing of filamin C increased the expression of matrix metallopeptidase 2 and improved the metastasis of prostate cancer in a zebrafish model. High filamin C associated with better prognosis of prostate cancer, leukemia and breast cancer patients. These findings establish a functional role of filamin C in human cancers and these data will be valuable for further study of its mechanisms.

Show MeSH
Related in: MedlinePlus