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Ubiquitin E3 ligase MARCH7 promotes ovarian tumor growth.

Hu J, Meng Y, Yu T, Hu L, Mao M - Oncotarget (2015)

Bottom Line: We found that expression of MARCH7 was higher in ovarian cancer tissues than normal ovarian tissues.Finally, MARCH7 was regulated by miR-101.Thus, MARCH7 is oncogenic and a potential target (oncotarget) for ovarian cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

ABSTRACT
Ubiquitin E3 ligase MARCH7 is involved in T cell proliferation and neuronal development. We found that expression of MARCH7 was higher in ovarian cancer tissues than normal ovarian tissues. Silencing MARCH7 decreased cell proliferation, migration, and invasion. Ectopic expression of MARCH7 increased cell proliferation, migration and invasion. Silencing MARCH7 prevented ovarian cancer growth in mice. Silencing MARCH7 inhibited NFkB and Wnt/β-catenin pathway. In agreement, ectopically expressed MARCH7 activated NFkB and Wnt/β-catenin pathways. Finally, MARCH7 was regulated by miR-101. Thus, MARCH7 is oncogenic and a potential target (oncotarget) for ovarian cancer therapy.

No MeSH data available.


Related in: MedlinePlus

(A) The expression of NFkB P65, NFkB P50, and β-catenin was detected by immunofluorescence staining in ovarian cancer SKOV3 cells (LV3-shMARCH7-1 or LV3-shMARCH7-2 infected) and A2780 cells (LV5-MARCH7 infected). (B). The nuclear translocation of NFkB P65, NFkB P50, and β-catenin was decreased in LV3-shMARCH7-1 or LV3-shMARCH7-2 infected ovarian cancer SKOV3 cells as compared with LV3-NC infected cells. The nuclear translocation of NFkB P65, NFkB P50, and β-catenin was increased in LV5-MARCH7 infected ovarian cancer A2780 cells compared with LV5-GFP infected cells. Original magnification ×200. Data are expressed as Mean ± SD from three independent experiments. * p < 0.05, and **p < 0.001.
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Figure 5: (A) The expression of NFkB P65, NFkB P50, and β-catenin was detected by immunofluorescence staining in ovarian cancer SKOV3 cells (LV3-shMARCH7-1 or LV3-shMARCH7-2 infected) and A2780 cells (LV5-MARCH7 infected). (B). The nuclear translocation of NFkB P65, NFkB P50, and β-catenin was decreased in LV3-shMARCH7-1 or LV3-shMARCH7-2 infected ovarian cancer SKOV3 cells as compared with LV3-NC infected cells. The nuclear translocation of NFkB P65, NFkB P50, and β-catenin was increased in LV5-MARCH7 infected ovarian cancer A2780 cells compared with LV5-GFP infected cells. Original magnification ×200. Data are expressed as Mean ± SD from three independent experiments. * p < 0.05, and **p < 0.001.

Mentions: The silencing of MARCH7 in SKOV3 cells caused a marked decrease in NF-κB luciferase activity (P<0.05), that was consistent with the above results (Fig. S1E). P65 and P50 protein levels were decreased in SKOV3 cells when MARCH7 was silenced (Fig. 4B(I)). Ectopic MARCH7 gene expression in A2780 cells increased the protein level P65 and P50 (Fig. 4B(II)). We tested whether MARCH7 regulated nuclear localization of individual NF-κB in ovarian cancer cells such as SKOV3 and A2780. The decrease in nuclear translocation of NF kB p65 and P50 after transfection to SKOV3 cells were observed with LV3-shMARCH7-1 or LV3-shMARCH7-2 as compared to that of LV3-NC (P<0.05) (Fig. 5A and 5B). Increase in nuclear translocation of NF kB p65 and P50 were observed after infection of A2780 cells with LV5-MARCH7 as compared with that of LV5-GFP (P < 0.05) (Fig. 5A and 5B).


Ubiquitin E3 ligase MARCH7 promotes ovarian tumor growth.

Hu J, Meng Y, Yu T, Hu L, Mao M - Oncotarget (2015)

(A) The expression of NFkB P65, NFkB P50, and β-catenin was detected by immunofluorescence staining in ovarian cancer SKOV3 cells (LV3-shMARCH7-1 or LV3-shMARCH7-2 infected) and A2780 cells (LV5-MARCH7 infected). (B). The nuclear translocation of NFkB P65, NFkB P50, and β-catenin was decreased in LV3-shMARCH7-1 or LV3-shMARCH7-2 infected ovarian cancer SKOV3 cells as compared with LV3-NC infected cells. The nuclear translocation of NFkB P65, NFkB P50, and β-catenin was increased in LV5-MARCH7 infected ovarian cancer A2780 cells compared with LV5-GFP infected cells. Original magnification ×200. Data are expressed as Mean ± SD from three independent experiments. * p < 0.05, and **p < 0.001.
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Figure 5: (A) The expression of NFkB P65, NFkB P50, and β-catenin was detected by immunofluorescence staining in ovarian cancer SKOV3 cells (LV3-shMARCH7-1 or LV3-shMARCH7-2 infected) and A2780 cells (LV5-MARCH7 infected). (B). The nuclear translocation of NFkB P65, NFkB P50, and β-catenin was decreased in LV3-shMARCH7-1 or LV3-shMARCH7-2 infected ovarian cancer SKOV3 cells as compared with LV3-NC infected cells. The nuclear translocation of NFkB P65, NFkB P50, and β-catenin was increased in LV5-MARCH7 infected ovarian cancer A2780 cells compared with LV5-GFP infected cells. Original magnification ×200. Data are expressed as Mean ± SD from three independent experiments. * p < 0.05, and **p < 0.001.
Mentions: The silencing of MARCH7 in SKOV3 cells caused a marked decrease in NF-κB luciferase activity (P<0.05), that was consistent with the above results (Fig. S1E). P65 and P50 protein levels were decreased in SKOV3 cells when MARCH7 was silenced (Fig. 4B(I)). Ectopic MARCH7 gene expression in A2780 cells increased the protein level P65 and P50 (Fig. 4B(II)). We tested whether MARCH7 regulated nuclear localization of individual NF-κB in ovarian cancer cells such as SKOV3 and A2780. The decrease in nuclear translocation of NF kB p65 and P50 after transfection to SKOV3 cells were observed with LV3-shMARCH7-1 or LV3-shMARCH7-2 as compared to that of LV3-NC (P<0.05) (Fig. 5A and 5B). Increase in nuclear translocation of NF kB p65 and P50 were observed after infection of A2780 cells with LV5-MARCH7 as compared with that of LV5-GFP (P < 0.05) (Fig. 5A and 5B).

Bottom Line: We found that expression of MARCH7 was higher in ovarian cancer tissues than normal ovarian tissues.Finally, MARCH7 was regulated by miR-101.Thus, MARCH7 is oncogenic and a potential target (oncotarget) for ovarian cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

ABSTRACT
Ubiquitin E3 ligase MARCH7 is involved in T cell proliferation and neuronal development. We found that expression of MARCH7 was higher in ovarian cancer tissues than normal ovarian tissues. Silencing MARCH7 decreased cell proliferation, migration, and invasion. Ectopic expression of MARCH7 increased cell proliferation, migration and invasion. Silencing MARCH7 prevented ovarian cancer growth in mice. Silencing MARCH7 inhibited NFkB and Wnt/β-catenin pathway. In agreement, ectopically expressed MARCH7 activated NFkB and Wnt/β-catenin pathways. Finally, MARCH7 was regulated by miR-101. Thus, MARCH7 is oncogenic and a potential target (oncotarget) for ovarian cancer therapy.

No MeSH data available.


Related in: MedlinePlus