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Hiwi Promotes the Proliferation of Colorectal Cancer Cells via Upregulating Global DNA Methylation.

Yang L, Bi L, Liu Q, Zhao M, Cao B, Li D, Xiu J - Dis. Markers (2015)

Bottom Line: Moreover, the Hiwi overexpression with an adenovirus vector significantly promoted the proliferation of Caro-2 and HT-29 cells, associated with significant increase in the global DNA methylation levels.And the chemical inhibition of DNA methylation significantly restrained such proliferation promotion.Our results imply for the first time that Hiwi promotes the proliferation of CRC cells via promoting global DNA methylation.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.

ABSTRACT
Hiwi is well known for its role in stem cell renewal, maintaining the resting stage, and downregulating cell cycle of stem cells via RNA silencing. And Hiwi overexpression has been recognized in several types of cancers. In the present study, we examined the Hiwi expression in colorectal cancer (CRC) specimens in both mRNA and protein levels via real-time quantitative PCR, western blot assay, and immunohistochemical staining. Then we explored the role of Hiwi in the cancer cell proliferation and in the DNA methylation in human CRC Caro-2 and HT-29 cell lines. Results demonstrated that both mRNA and protein levels of Hiwi were significantly higher in 38 CRC tissues than in 38 peritumor tissues. Moreover, the Hiwi overexpression with an adenovirus vector significantly promoted the proliferation of Caro-2 and HT-29 cells, associated with significant increase in the global DNA methylation levels. And the chemical inhibition of DNA methylation significantly restrained such proliferation promotion. In summary, we confirmed that Hiwi was overexpressed in CRC tissues and that the forced Hiwi overexpression promoted the proliferation and global DNA methylation of CRC cell lines. Our results imply for the first time that Hiwi promotes the proliferation of CRC cells via promoting global DNA methylation.

No MeSH data available.


Related in: MedlinePlus

Global genomic methylation level in Caco-2 or HT-29 cells post-Ad-Hiwi or Ad-RFP infection. (a) and (c): time-dependence DNA methylation levels in Caco-2 cells (a) or HT-29 (c) cells, after being infected with Ad-Hiwi or Ad-RFP viruses. (b) and (d): dose-dependence of the methylation promotion by the Ad-Hiwi infection (0, 1, or 10 MOI) in Caco-2 cells (b) or HT-29 (d) cells, with the infection with 10 MOI Ad-RFP as control.
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fig4: Global genomic methylation level in Caco-2 or HT-29 cells post-Ad-Hiwi or Ad-RFP infection. (a) and (c): time-dependence DNA methylation levels in Caco-2 cells (a) or HT-29 (c) cells, after being infected with Ad-Hiwi or Ad-RFP viruses. (b) and (d): dose-dependence of the methylation promotion by the Ad-Hiwi infection (0, 1, or 10 MOI) in Caco-2 cells (b) or HT-29 (d) cells, with the infection with 10 MOI Ad-RFP as control.

Mentions: To investigate the association of the growth promotion by Hiwi overexpression with the DNA methylation in CRC cells, we then evaluated the global DNA methylation in the Ad-Hiwi- or Ad-RFP-infected CRC cells. The global DNA methylation fold change in Caco-2 or HT-29 cells after Ad-Hiwi or Ad-RFP infection is shown in Figure 4. There was significant difference of the DNA methylation level between the Ad-Hiwi- and Ad-RFP-infected Caco-2 (Figures 4(a) and 4(b)) or between the Ad-Hiwi- and Ad-RFP-infected HT-29 cells (Figures 4(c) and 4(d)). There was no difference between the blank and Ad-RFP infected Caco-2 or HT-29 cells. And what is more, there was a dose dependence in the DNA methylation promotion by the Ad-Hiwi infection. The fold change of global DNA methylation in Caco-2 or in HT-29 cells was higher after the infection with Ad-Hiwi at 10 MOI than at 1 MOI (Figures 4(b) and 4(d); p < 0.05 resp.). These findings showed that DNA methylation level in CRC cells was significantly associated with the Hiwi overexpression.


Hiwi Promotes the Proliferation of Colorectal Cancer Cells via Upregulating Global DNA Methylation.

Yang L, Bi L, Liu Q, Zhao M, Cao B, Li D, Xiu J - Dis. Markers (2015)

Global genomic methylation level in Caco-2 or HT-29 cells post-Ad-Hiwi or Ad-RFP infection. (a) and (c): time-dependence DNA methylation levels in Caco-2 cells (a) or HT-29 (c) cells, after being infected with Ad-Hiwi or Ad-RFP viruses. (b) and (d): dose-dependence of the methylation promotion by the Ad-Hiwi infection (0, 1, or 10 MOI) in Caco-2 cells (b) or HT-29 (d) cells, with the infection with 10 MOI Ad-RFP as control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4556077&req=5

fig4: Global genomic methylation level in Caco-2 or HT-29 cells post-Ad-Hiwi or Ad-RFP infection. (a) and (c): time-dependence DNA methylation levels in Caco-2 cells (a) or HT-29 (c) cells, after being infected with Ad-Hiwi or Ad-RFP viruses. (b) and (d): dose-dependence of the methylation promotion by the Ad-Hiwi infection (0, 1, or 10 MOI) in Caco-2 cells (b) or HT-29 (d) cells, with the infection with 10 MOI Ad-RFP as control.
Mentions: To investigate the association of the growth promotion by Hiwi overexpression with the DNA methylation in CRC cells, we then evaluated the global DNA methylation in the Ad-Hiwi- or Ad-RFP-infected CRC cells. The global DNA methylation fold change in Caco-2 or HT-29 cells after Ad-Hiwi or Ad-RFP infection is shown in Figure 4. There was significant difference of the DNA methylation level between the Ad-Hiwi- and Ad-RFP-infected Caco-2 (Figures 4(a) and 4(b)) or between the Ad-Hiwi- and Ad-RFP-infected HT-29 cells (Figures 4(c) and 4(d)). There was no difference between the blank and Ad-RFP infected Caco-2 or HT-29 cells. And what is more, there was a dose dependence in the DNA methylation promotion by the Ad-Hiwi infection. The fold change of global DNA methylation in Caco-2 or in HT-29 cells was higher after the infection with Ad-Hiwi at 10 MOI than at 1 MOI (Figures 4(b) and 4(d); p < 0.05 resp.). These findings showed that DNA methylation level in CRC cells was significantly associated with the Hiwi overexpression.

Bottom Line: Moreover, the Hiwi overexpression with an adenovirus vector significantly promoted the proliferation of Caro-2 and HT-29 cells, associated with significant increase in the global DNA methylation levels.And the chemical inhibition of DNA methylation significantly restrained such proliferation promotion.Our results imply for the first time that Hiwi promotes the proliferation of CRC cells via promoting global DNA methylation.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.

ABSTRACT
Hiwi is well known for its role in stem cell renewal, maintaining the resting stage, and downregulating cell cycle of stem cells via RNA silencing. And Hiwi overexpression has been recognized in several types of cancers. In the present study, we examined the Hiwi expression in colorectal cancer (CRC) specimens in both mRNA and protein levels via real-time quantitative PCR, western blot assay, and immunohistochemical staining. Then we explored the role of Hiwi in the cancer cell proliferation and in the DNA methylation in human CRC Caro-2 and HT-29 cell lines. Results demonstrated that both mRNA and protein levels of Hiwi were significantly higher in 38 CRC tissues than in 38 peritumor tissues. Moreover, the Hiwi overexpression with an adenovirus vector significantly promoted the proliferation of Caro-2 and HT-29 cells, associated with significant increase in the global DNA methylation levels. And the chemical inhibition of DNA methylation significantly restrained such proliferation promotion. In summary, we confirmed that Hiwi was overexpressed in CRC tissues and that the forced Hiwi overexpression promoted the proliferation and global DNA methylation of CRC cell lines. Our results imply for the first time that Hiwi promotes the proliferation of CRC cells via promoting global DNA methylation.

No MeSH data available.


Related in: MedlinePlus