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miR-372 down-regulates the oncogene ATAD2 to influence hepatocellular carcinoma proliferation and metastasis.

Wu G, Liu H, He H, Wang Y, Lu X, Yu Y, Xia S, Meng X, Liu Y - BMC Cancer (2014)

Bottom Line: In addition, ATAD2 knockdown was found to extremely up-regulate APC expression and down-regulate CTNNA1 at the mRNA level.The findings demonstrated that miR-372 suppressed the expression of ATAD2, which was highly expressed in HCC and exerted a proto-oncogene effect in hepatic carcinogenesis.In conclusion, ATAD2 may promote HCC progression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China. wugang@mail.cmu.edu.cn.

ABSTRACT

Background: ATAD2 is associated with many cellular processes, such as cell growth, migration and invasion. However, no studies have been conducted on the molecular biological function of the ATAD2 gene in hepatocellular carcinoma (HCC).

Methods: The protein and mRNA level expression of ATAD2 was examined in tissues and cell lines. Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression. ATAD2 knockdown was used to analyze cell proliferation and invasion. The upstream and downstream of ATAD2 was analyzed by RT2 Profiler™ PCR array and luciferasex fluorescence system.

Results: ATAD2 was highly expressed in liver cancer samples and correlated with poor survival. High ATAD2 expression was positively correlated with metastasis (P = 0.005) and was an independent prognostic factor in HCC (P = 0.001). ATAD2 depletion by RNA interference reduced their capacity for invasion and proliferation and led to a G1 phase arrest in vitro. Further study revealed that miR-372 was an upstream target of ATAD2 as miR-372 was bound directly to its 3' untranslated region (3' UTR). In addition, ATAD2 knockdown was found to extremely up-regulate APC expression and down-regulate CTNNA1 at the mRNA level.

Conclusions: The findings demonstrated that miR-372 suppressed the expression of ATAD2, which was highly expressed in HCC and exerted a proto-oncogene effect in hepatic carcinogenesis. In conclusion, ATAD2 may promote HCC progression.

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Related in: MedlinePlus

The CCK8 assay was performed after ATAD2 siRNA treatment. (a) A reduction of absorbance was observed (P < 0.05). (b) Clonogenic assays were performed with ATAD2-depleted cancer cells. The number of colonies formed by cells treated with ATAD2 siRNA was far fewer than that of control siRNA-treated cells (P < 0.05).
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Figure 3: The CCK8 assay was performed after ATAD2 siRNA treatment. (a) A reduction of absorbance was observed (P < 0.05). (b) Clonogenic assays were performed with ATAD2-depleted cancer cells. The number of colonies formed by cells treated with ATAD2 siRNA was far fewer than that of control siRNA-treated cells (P < 0.05).

Mentions: A significant reduction in the proliferation rate was observed with the CCK8 assay 2 days after transfection with ATAD2 siRNA when compared to negative control siRNA (Figure 3a). Consistent with the CCK8 assay, the depletion of ATAD2 in Huh7 (Neg. siRNA vs. ATAD2 siRNA: 124 ± 16 vs. 36 ± 10, P < 0.001) and HCCLM3 (Neg. siRNA vs. ATAD2 siRNA: 102 ± 22 vs. 39 ± 13, P < 0.001) cells led to a significant reduction in the number and size of foci (Figure 3b). The DNA content determined using flow cytometry demonstrated that ATAD2 siRNA transfection increased the percentage of cells in G1 phase and decreased those in the S phase in both cell lines (Figure 4).


miR-372 down-regulates the oncogene ATAD2 to influence hepatocellular carcinoma proliferation and metastasis.

Wu G, Liu H, He H, Wang Y, Lu X, Yu Y, Xia S, Meng X, Liu Y - BMC Cancer (2014)

The CCK8 assay was performed after ATAD2 siRNA treatment. (a) A reduction of absorbance was observed (P < 0.05). (b) Clonogenic assays were performed with ATAD2-depleted cancer cells. The number of colonies formed by cells treated with ATAD2 siRNA was far fewer than that of control siRNA-treated cells (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4016509&req=5

Figure 3: The CCK8 assay was performed after ATAD2 siRNA treatment. (a) A reduction of absorbance was observed (P < 0.05). (b) Clonogenic assays were performed with ATAD2-depleted cancer cells. The number of colonies formed by cells treated with ATAD2 siRNA was far fewer than that of control siRNA-treated cells (P < 0.05).
Mentions: A significant reduction in the proliferation rate was observed with the CCK8 assay 2 days after transfection with ATAD2 siRNA when compared to negative control siRNA (Figure 3a). Consistent with the CCK8 assay, the depletion of ATAD2 in Huh7 (Neg. siRNA vs. ATAD2 siRNA: 124 ± 16 vs. 36 ± 10, P < 0.001) and HCCLM3 (Neg. siRNA vs. ATAD2 siRNA: 102 ± 22 vs. 39 ± 13, P < 0.001) cells led to a significant reduction in the number and size of foci (Figure 3b). The DNA content determined using flow cytometry demonstrated that ATAD2 siRNA transfection increased the percentage of cells in G1 phase and decreased those in the S phase in both cell lines (Figure 4).

Bottom Line: In addition, ATAD2 knockdown was found to extremely up-regulate APC expression and down-regulate CTNNA1 at the mRNA level.The findings demonstrated that miR-372 suppressed the expression of ATAD2, which was highly expressed in HCC and exerted a proto-oncogene effect in hepatic carcinogenesis.In conclusion, ATAD2 may promote HCC progression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China. wugang@mail.cmu.edu.cn.

ABSTRACT

Background: ATAD2 is associated with many cellular processes, such as cell growth, migration and invasion. However, no studies have been conducted on the molecular biological function of the ATAD2 gene in hepatocellular carcinoma (HCC).

Methods: The protein and mRNA level expression of ATAD2 was examined in tissues and cell lines. Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression. ATAD2 knockdown was used to analyze cell proliferation and invasion. The upstream and downstream of ATAD2 was analyzed by RT2 Profiler™ PCR array and luciferasex fluorescence system.

Results: ATAD2 was highly expressed in liver cancer samples and correlated with poor survival. High ATAD2 expression was positively correlated with metastasis (P = 0.005) and was an independent prognostic factor in HCC (P = 0.001). ATAD2 depletion by RNA interference reduced their capacity for invasion and proliferation and led to a G1 phase arrest in vitro. Further study revealed that miR-372 was an upstream target of ATAD2 as miR-372 was bound directly to its 3' untranslated region (3' UTR). In addition, ATAD2 knockdown was found to extremely up-regulate APC expression and down-regulate CTNNA1 at the mRNA level.

Conclusions: The findings demonstrated that miR-372 suppressed the expression of ATAD2, which was highly expressed in HCC and exerted a proto-oncogene effect in hepatic carcinogenesis. In conclusion, ATAD2 may promote HCC progression.

Show MeSH
Related in: MedlinePlus