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MicroRNA-200a suppresses metastatic potential of side population cells in human hepatocellular carcinoma by decreasing ZEB2.

Yang X, Wang J, Qu S, Zhang H, Ruan B, Gao Y, Ma B, Wang X, Wu N, Li X, Dou K, Li H - Oncotarget (2015)

Bottom Line: We found that miR-200a was downregulated in HCC/SP and this was associated metastasis.Overexpression of miR-200a in SP cells decreased metastasis-related markers and expression of ZEB2.The associations between miR-200a, SP cells and ZEB2 were validated in HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical Uiversity, Xi'an, China.

ABSTRACT
Although microRNA-200a (miR-200a) is frequently downregulated in cancer, its role in side population (SP) has not been investigated. In this study, 101 pairs of primary hepatocellular carcinoma (HCC) tissues and matched normal control tissues were analyzed for miR-200a expression and its clinicopathological value was determined. We found that miR-200a was downregulated in HCC/SP and this was associated metastasis. MiR-200a suppressed metastasis of SP cells. Overexpression of miR-200a in SP cells decreased metastasis-related markers and expression of ZEB2. The associations between miR-200a, SP cells and ZEB2 were validated in HCC. These findings reveal that miR-200a suppresses metastasis of SP cells by downregulating ZEB2.

No MeSH data available.


Related in: MedlinePlus

In vivo metastasis assays(A) Representative bioluminescent imaging (BLI) at 8 weeks is shown for the different groups. (B) The incidence of lung metastases in nude mice. (C) The intensity of luminescence in the different groups. (D) The number of metastatic nodules on the surface of the lungs in mice from the different groups. (E) Representative H&E staining of lung tissues is shown. (F) The overall survival of the nude mice. (G) An immunohistochemical analysis of miR-200a, ZEB2, and E-cadherin expression in metastatic nodules. *p < 0.05, **p < 0.01, t test.
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Figure 6: In vivo metastasis assays(A) Representative bioluminescent imaging (BLI) at 8 weeks is shown for the different groups. (B) The incidence of lung metastases in nude mice. (C) The intensity of luminescence in the different groups. (D) The number of metastatic nodules on the surface of the lungs in mice from the different groups. (E) Representative H&E staining of lung tissues is shown. (F) The overall survival of the nude mice. (G) An immunohistochemical analysis of miR-200a, ZEB2, and E-cadherin expression in metastatic nodules. *p < 0.05, **p < 0.01, t test.

Mentions: SP cells were injected into the caudal vein of nude mice. Representative bioluminescent imaging (BLI) at 8 weeks is shown for the different groups (Fig. 6A). The in vivo metastatic assay showed that the upregulation of miR-200a decreased the incidence of lung metastasis and the number of metastatic lung nodules on the surface, but increased the overall survival time in the MHCC-97H-SP-miR-200a group. In contrast, the down-regulation of miR-200a increased the incidence of lung metastasis and the number of metastatic lung nodules on the surface but decreased the overall survival time in the Huh7-SP-KD-miR-200a group (Fig. 6B,C,D,F). Representative hematoxylin and eosin (H&E) staining showed that metastatic nodules were observed in the lungs of mice in the MHCC-97H-SP-Control group. There were no obvious metastatic nodules in the lungs of mice in the MHCC-97H-SP-miR-200a group. In contrast, metastatic nodules were observed in the lungs of mice in the Huh7-SP-KD-miR-200a group, whereas no metastatic nodules were found in mice in the Huh7-SP-KD-Control group (Fig. 6E). In addition, immunohistochemistry revealed that miR-200a expression was inversely correlated with ZEB2 expression but was positively correlated with E-cadherin expression (Fig. 6G).


MicroRNA-200a suppresses metastatic potential of side population cells in human hepatocellular carcinoma by decreasing ZEB2.

Yang X, Wang J, Qu S, Zhang H, Ruan B, Gao Y, Ma B, Wang X, Wu N, Li X, Dou K, Li H - Oncotarget (2015)

In vivo metastasis assays(A) Representative bioluminescent imaging (BLI) at 8 weeks is shown for the different groups. (B) The incidence of lung metastases in nude mice. (C) The intensity of luminescence in the different groups. (D) The number of metastatic nodules on the surface of the lungs in mice from the different groups. (E) Representative H&E staining of lung tissues is shown. (F) The overall survival of the nude mice. (G) An immunohistochemical analysis of miR-200a, ZEB2, and E-cadherin expression in metastatic nodules. *p < 0.05, **p < 0.01, t test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480725&req=5

Figure 6: In vivo metastasis assays(A) Representative bioluminescent imaging (BLI) at 8 weeks is shown for the different groups. (B) The incidence of lung metastases in nude mice. (C) The intensity of luminescence in the different groups. (D) The number of metastatic nodules on the surface of the lungs in mice from the different groups. (E) Representative H&E staining of lung tissues is shown. (F) The overall survival of the nude mice. (G) An immunohistochemical analysis of miR-200a, ZEB2, and E-cadherin expression in metastatic nodules. *p < 0.05, **p < 0.01, t test.
Mentions: SP cells were injected into the caudal vein of nude mice. Representative bioluminescent imaging (BLI) at 8 weeks is shown for the different groups (Fig. 6A). The in vivo metastatic assay showed that the upregulation of miR-200a decreased the incidence of lung metastasis and the number of metastatic lung nodules on the surface, but increased the overall survival time in the MHCC-97H-SP-miR-200a group. In contrast, the down-regulation of miR-200a increased the incidence of lung metastasis and the number of metastatic lung nodules on the surface but decreased the overall survival time in the Huh7-SP-KD-miR-200a group (Fig. 6B,C,D,F). Representative hematoxylin and eosin (H&E) staining showed that metastatic nodules were observed in the lungs of mice in the MHCC-97H-SP-Control group. There were no obvious metastatic nodules in the lungs of mice in the MHCC-97H-SP-miR-200a group. In contrast, metastatic nodules were observed in the lungs of mice in the Huh7-SP-KD-miR-200a group, whereas no metastatic nodules were found in mice in the Huh7-SP-KD-Control group (Fig. 6E). In addition, immunohistochemistry revealed that miR-200a expression was inversely correlated with ZEB2 expression but was positively correlated with E-cadherin expression (Fig. 6G).

Bottom Line: We found that miR-200a was downregulated in HCC/SP and this was associated metastasis.Overexpression of miR-200a in SP cells decreased metastasis-related markers and expression of ZEB2.The associations between miR-200a, SP cells and ZEB2 were validated in HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical Uiversity, Xi'an, China.

ABSTRACT
Although microRNA-200a (miR-200a) is frequently downregulated in cancer, its role in side population (SP) has not been investigated. In this study, 101 pairs of primary hepatocellular carcinoma (HCC) tissues and matched normal control tissues were analyzed for miR-200a expression and its clinicopathological value was determined. We found that miR-200a was downregulated in HCC/SP and this was associated metastasis. MiR-200a suppressed metastasis of SP cells. Overexpression of miR-200a in SP cells decreased metastasis-related markers and expression of ZEB2. The associations between miR-200a, SP cells and ZEB2 were validated in HCC. These findings reveal that miR-200a suppresses metastasis of SP cells by downregulating ZEB2.

No MeSH data available.


Related in: MedlinePlus