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Research Papers

Factor inhibiting HIF1α (FIH-1) functions as a tumor suppressor in human colorectal cancer by repressing HIF1α pathway

, , , , , , & show all
Pages 244-252 | Received 24 Aug 2014, Accepted 18 Dec 2014, Published online: 10 Mar 2015

Figures & data

Figure 1. FIH-1 is downregulated in human CRC tissues and is a predictor for CRC prognosis. (A) Protein level of FIH-1 expression was significantly decreased in CRC tissues comparing with their corresponding nontumor tissues. (B) Downregulation of FIH-1 defined a poor prognosis of CRC.

Figure 1. FIH-1 is downregulated in human CRC tissues and is a predictor for CRC prognosis. (A) Protein level of FIH-1 expression was significantly decreased in CRC tissues comparing with their corresponding nontumor tissues. (B) Downregulation of FIH-1 defined a poor prognosis of CRC.

Table 1. Clinicopathologic correlation of FIH-1 down-regulation in human CRCs

Figure 2. Decreased FIH-1 expression in CRC tissue is associated with disease progression. (A) FIH-1 expression pattern in T2N0M0 stage CRC sample. (B) FIH-1 expression pattern in T3 stage CRC sample. (C) FIH-1 expression pattern in N2 stage CRC sample. (D) FIH-1 expression pattern in M1 stage CRC sample. (E) Low mRNA level of FIH-1 expression was significantly correlated with CRC invading depth, lymph node involvement, and metastasis.

Figure 2. Decreased FIH-1 expression in CRC tissue is associated with disease progression. (A) FIH-1 expression pattern in T2N0M0 stage CRC sample. (B) FIH-1 expression pattern in T3 stage CRC sample. (C) FIH-1 expression pattern in N2 stage CRC sample. (D) FIH-1 expression pattern in M1 stage CRC sample. (E) Low mRNA level of FIH-1 expression was significantly correlated with CRC invading depth, lymph node involvement, and metastasis.

Figure 3. Effect of FIH-1 overexpression on proliferation, migration, invasion of LOVO and SW1116 cells. (A) Overexpression of FIH-1 had significant effect on decreasing proliferation rate of both LOVO and SW1116 cell lines. (B) Wound closure was delayed in cells transfected with FIH-1 overexpression plasmidbitorfunctional assays. We 31 can directly regulate FIH-1 expression in both CRC tissue and cell lines. Next we examined th as compared with negative control in 18 h time points in both types of CRC cells. (C) Representative fields of migration (up) or invasion (down) cells on the membrane were on the left. Average migration or invasion cell number per field was on the right. The migration or invasion cell number of LOVO or SW1116 transfected with FIH-1 overexpression plasmidbitorfunctional assays. We 31 can directly regulate FIH-1 expression in both CRC tissue and cell lines. Next we examined th was drastically decreased. (D) The number of clones of LOVO or SW1116 transfected with FIH-1 overexpression plasmid was fewer than that of control cells.

Figure 3. Effect of FIH-1 overexpression on proliferation, migration, invasion of LOVO and SW1116 cells. (A) Overexpression of FIH-1 had significant effect on decreasing proliferation rate of both LOVO and SW1116 cell lines. (B) Wound closure was delayed in cells transfected with FIH-1 overexpression plasmidbitorfunctional assays. We 31 can directly regulate FIH-1 expression in both CRC tissue and cell lines. Next we examined th as compared with negative control in 18 h time points in both types of CRC cells. (C) Representative fields of migration (up) or invasion (down) cells on the membrane were on the left. Average migration or invasion cell number per field was on the right. The migration or invasion cell number of LOVO or SW1116 transfected with FIH-1 overexpression plasmidbitorfunctional assays. We 31 can directly regulate FIH-1 expression in both CRC tissue and cell lines. Next we examined th was drastically decreased. (D) The number of clones of LOVO or SW1116 transfected with FIH-1 overexpression plasmid was fewer than that of control cells.

Figure 4. Increased FIH-1 decreases GLUT-1 and VEGF expression levels in LOVO and SW1116. (A) Increased FIH-1 significantly decreased GLUT-1 and VEGF mRNA levels in LOVO cells, but did not affect HIF-1α mRNA level. (B) Increased FIH-1 decreased GLUT-1 and VEGF protein levels in LOVO cells, but did not affect HIF-1α protein level. (C) Increased FIH-1 significantly decreased GLUT-1 and VEGF mRNA levels in SW1116 cells, but did not affect HIF-1α mRNA level. (D) Increased FIH-1 decreased GLUT-1 and VEGF protein levels in SW1116 cells, but did not affect HIF-1α protein level.

Figure 4. Increased FIH-1 decreases GLUT-1 and VEGF expression levels in LOVO and SW1116. (A) Increased FIH-1 significantly decreased GLUT-1 and VEGF mRNA levels in LOVO cells, but did not affect HIF-1α mRNA level. (B) Increased FIH-1 decreased GLUT-1 and VEGF protein levels in LOVO cells, but did not affect HIF-1α protein level. (C) Increased FIH-1 significantly decreased GLUT-1 and VEGF mRNA levels in SW1116 cells, but did not affect HIF-1α mRNA level. (D) Increased FIH-1 decreased GLUT-1 and VEGF protein levels in SW1116 cells, but did not affect HIF-1α protein level.

Figure 5. FIH-1 controls the tumor growth of LOVO xenografts in vivo. (A) Overexpression of FIH-1 strikingly decreased the growth of LOVO cells xenografted in nude mice. (B) The tumors were significantly bigger in control group than those in treated group. (C) The tumors were significantly heavier in control group than those in treated group. (D) The protein expression levels of FIH-1, GLUT-1, and VEGF in the subcutaneous tumor tissues collected from control and treated groups were detected by IHC.

Figure 5. FIH-1 controls the tumor growth of LOVO xenografts in vivo. (A) Overexpression of FIH-1 strikingly decreased the growth of LOVO cells xenografted in nude mice. (B) The tumors were significantly bigger in control group than those in treated group. (C) The tumors were significantly heavier in control group than those in treated group. (D) The protein expression levels of FIH-1, GLUT-1, and VEGF in the subcutaneous tumor tissues collected from control and treated groups were detected by IHC.

Figure 6. Schematic of the described interaction between FIH-1 and HIF-1α, along with a brief description of the portion of the HIF-1α pathway mentioned in the article.

Figure 6. Schematic of the described interaction between FIH-1 and HIF-1α, along with a brief description of the portion of the HIF-1α pathway mentioned in the article.

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