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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

Functional analysis of miR-200a in vitro(A) MiR-200a expression in a subpopulation in human HCC cell lines. (B) Expression of miR-200a following transfection was confirmed by qRT-PCR. (C) Relative mRNA expression of metastasis-related markers in groups with and without miR-200a induction. (D) Cell invasion assay: (upper panel, representative images of invasion assay; bottom panel, quantification of cell number); Cell migration assay: (upper panel, representative images of migration assay; bottom panel, quantification of cell number). *p < 0.05, **p < 0.01, t test.
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Figure 5: Functional analysis of miR-200a in vitro(A) MiR-200a expression in a subpopulation in human HCC cell lines. (B) Expression of miR-200a following transfection was confirmed by qRT-PCR. (C) Relative mRNA expression of metastasis-related markers in groups with and without miR-200a induction. (D) Cell invasion assay: (upper panel, representative images of invasion assay; bottom panel, quantification of cell number); Cell migration assay: (upper panel, representative images of migration assay; bottom panel, quantification of cell number). *p < 0.05, **p < 0.01, t test.

Mentions: The index of miR-200a expression in SP cells of MHCC-97H and Huh7 was significantly lower than that in NSP cells from both the MHCC-97H and Huh7 cell lines (Fig. 5A). Expression of miR-200a after transfection was confirmed by qRT-PCR (Fig. 5B). Expression of metastasis-related markers was confirmed by qRT-PCR after transfection (Fig. 5C). E-cadherin and ZO-1 were over-expressed in the MHCC-97H-SP-miR-200a group but were weakly-expressed in the Huh7-SP-KD-miR-200a group. In contrast, the expression values of N-cadherin, VASP, LAMC2 and ZEB2 were opposite to those observed for the other above-mentioned genes. The upregulation of miR-200a expression decreased the ability of the MHCC-97H-SP cells to invade and migrate. Conversely, the inhibition of miR-200a expression in Huh7-SP cells enhanced the ability of the SP cells to invade and migrate (Fig. 5D).


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)

Functional analysis of miR-200a in vitro(A) MiR-200a expression in a subpopulation in human HCC cell lines. (B) Expression of miR-200a following transfection was confirmed by qRT-PCR. (C) Relative mRNA expression of metastasis-related markers in groups with and without miR-200a induction. (D) Cell invasion assay: (upper panel, representative images of invasion assay; bottom panel, quantification of cell number); Cell migration assay: (upper panel, representative images of migration assay; bottom panel, quantification of cell number). *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 5: Functional analysis of miR-200a in vitro(A) MiR-200a expression in a subpopulation in human HCC cell lines. (B) Expression of miR-200a following transfection was confirmed by qRT-PCR. (C) Relative mRNA expression of metastasis-related markers in groups with and without miR-200a induction. (D) Cell invasion assay: (upper panel, representative images of invasion assay; bottom panel, quantification of cell number); Cell migration assay: (upper panel, representative images of migration assay; bottom panel, quantification of cell number). *p < 0.05, **p < 0.01, t test.
Mentions: The index of miR-200a expression in SP cells of MHCC-97H and Huh7 was significantly lower than that in NSP cells from both the MHCC-97H and Huh7 cell lines (Fig. 5A). Expression of miR-200a after transfection was confirmed by qRT-PCR (Fig. 5B). Expression of metastasis-related markers was confirmed by qRT-PCR after transfection (Fig. 5C). E-cadherin and ZO-1 were over-expressed in the MHCC-97H-SP-miR-200a group but were weakly-expressed in the Huh7-SP-KD-miR-200a group. In contrast, the expression values of N-cadherin, VASP, LAMC2 and ZEB2 were opposite to those observed for the other above-mentioned genes. The upregulation of miR-200a expression decreased the ability of the MHCC-97H-SP cells to invade and migrate. Conversely, the inhibition of miR-200a expression in Huh7-SP cells enhanced the ability of the SP cells to invade and migrate (Fig. 5D).

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