Objective: This study was designed to investigate differential pattern of G1-cyclins (D1 and E) in transitional cell carcinoma (TCC) of human urinary bladder with or without human papillomavirus-18 (HPV-18) infection....Objective: This study was designed to investigate differential pattern of G1-cyclins (D1 and E) in transitional cell carcinoma (TCC) of human urinary bladder with or without human papillomavirus-18 (HPV-18) infection. Methods: Immunohistochemistry method was used in the detection of the expression of G1-cyclins in 57 cases of TCC (7 normal bladders as control), and HPV-18 DNA was found in 29 cases by polymerases chain reaction (PCR). Results: Cyclin D1 expression was found in 41 of 57 (71.93%) TCCs and it was reverse associated with HPV (x 2=8.21, P<0.05). And cyclin D1 expression was found in 16 of 29 (55.17%) in HPV-18 infection group and 25 of 28 (89.29%) in non-HPV infection group. Cyclin E expression was detected in 36 of 57 (63.16%) and the association between the cyclin E expression and HPV infection was not found (x2=0.52, P>0.05). Cyclin E expression was found in 17 of 29 (56.82%) in HPV-18 infection group and 19 of 28 (67.86%) in non-HPV infection group. There was obvious difference in the cyclin D1 and cyclin E expression between the TCC and normal tissue (x 2=7.46, P<0.05; x 2=7.45, P<0.05, respectively). Conclusion: These data demonstrated that HPV infection altered the control of G1 cell cycle. And changes of G1 cell cycle regulatory proteins, either by interaction of cellular protein with viral oncoproteins or by changes in the cellular proteins themselves, may be critical for carcinogenesis of TCC of urinary bladder.展开更多
HL-60 cells were synchronized from G1 to S phase boundary with a double thymidine block. Samples of the cells were collected at scheduled time points after the release of the block. It was found with immunoblot analys...HL-60 cells were synchronized from G1 to S phase boundary with a double thymidine block. Samples of the cells were collected at scheduled time points after the release of the block. It was found with immunoblot analysis that the protein expression of cyclin E and D, fluctuated periodically. They both began to increase in G, phase,reached the peak in S phase and declined gradually in G, phase. The protein expression of cyclin-dependent kinase P34cdk2 showed no periodical changes- The antiproliferation effect of retinoic acid or arotinoidethylester on HL-60cells was manifested by a block in Go/G1 of most of the cells and resulted in a marked decrease of the protein expression of cyclin E and D1 and no significant change of P34cdk2. These findings suggest that retinoic acid or arotinoidethylester is able to suppress the proliferation of HL-cells or to induce their differentiation.展开更多
The BLU gene coding for zinc finger,MYND-type containing 10(ZMYND10)protein is mapped on chromosomal region 3p21.It is frequently lost in some kinds of cancers due to hypermethylation on its promoter region and identi...The BLU gene coding for zinc finger,MYND-type containing 10(ZMYND10)protein is mapped on chromosomal region 3p21.It is frequently lost in some kinds of cancers due to hypermethylation on its promoter region and identified as a tumour suppressor gene.The underlying mechanisms for BLU-mediated tumor suppression remain unclear.BLU has been reported to disturb cell cycle progression.The present study aims at examining whether ZMYND10 prevents progression of the cell cycle by targeting to repressive histone marks and downregulating the level of cyclins.Proteins structurally similar with ZMYND10 have been shown to recognize DNA sequence upstream of coding portion of the gene encoding cell cycle regulators.Enzymes,notably demethylases modifying the lysine residues are over-expressed line oncoproteins,and targeted in anti-cancer therapy.BLU was re-expressed in H1299 and HepG2 cells.The level of cyclin D1,cyclin B1 and trimethylate lysine 9 on histone 3(H3K9me3)and the binding of BLU with SIN3A(a component of the co-repressor)were detected.Cell cycle profile was measured.The evolutionary relationship between ZMYND10 and other ZMYND proteins was analysed by phylogenetic tree construction.We found that BLU expression induced G1 arrest in H1299 cells,and induced G1/G2 arrest in HepG2 cells.Cell cycle arrest was correlated with reduced activities and levels of cyclins;cyclin D1 was downregulated in H1299 cells;Both cyclin B1 and D1 were downregulated in HepG2 cells;and that BLU was associated with SIN3A.In both cell lines,the expression of H3K9me3 was induced.BLU was clustered with histone methyltransferase SMYD3 and SMYD1 on the same clade of the deduced phylogenetic tree.The results thus suggested that ZMYND10 encoded by BLU inhibited cyclins activity to prevent cell cycle progression through interaction with repressors and histone repressive marks to block the expression of genes coding for cyclins.展开更多
BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a pot...BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.展开更多
The cyclin-dependent kinase inhibitor p21( waf1/cip1/sdi1) is an important negative regulator in control of cell cycle. Its functions of inhibiting cancer cell growth and its effects on expression of Gl phase cyclins ...The cyclin-dependent kinase inhibitor p21( waf1/cip1/sdi1) is an important negative regulator in control of cell cycle. Its functions of inhibiting cancer cell growth and its effects on expression of Gl phase cyclins and related CDKs are a worthy topic for study. The plasmid expressing p2l with high level was transformed to human breast cancer cells, and the expression of p2l in cells was enhanced, then the cell growth rate, anchorage-independent growth and tu-morigenecity were tested, at the same time the expression levels of cyclinD1, CDK4,展开更多
基金This work was supported by the National Natural Science Foundation of China (No. 39370291).
文摘Objective: This study was designed to investigate differential pattern of G1-cyclins (D1 and E) in transitional cell carcinoma (TCC) of human urinary bladder with or without human papillomavirus-18 (HPV-18) infection. Methods: Immunohistochemistry method was used in the detection of the expression of G1-cyclins in 57 cases of TCC (7 normal bladders as control), and HPV-18 DNA was found in 29 cases by polymerases chain reaction (PCR). Results: Cyclin D1 expression was found in 41 of 57 (71.93%) TCCs and it was reverse associated with HPV (x 2=8.21, P<0.05). And cyclin D1 expression was found in 16 of 29 (55.17%) in HPV-18 infection group and 25 of 28 (89.29%) in non-HPV infection group. Cyclin E expression was detected in 36 of 57 (63.16%) and the association between the cyclin E expression and HPV infection was not found (x2=0.52, P>0.05). Cyclin E expression was found in 17 of 29 (56.82%) in HPV-18 infection group and 19 of 28 (67.86%) in non-HPV infection group. There was obvious difference in the cyclin D1 and cyclin E expression between the TCC and normal tissue (x 2=7.46, P<0.05; x 2=7.45, P<0.05, respectively). Conclusion: These data demonstrated that HPV infection altered the control of G1 cell cycle. And changes of G1 cell cycle regulatory proteins, either by interaction of cellular protein with viral oncoproteins or by changes in the cellular proteins themselves, may be critical for carcinogenesis of TCC of urinary bladder.
文摘HL-60 cells were synchronized from G1 to S phase boundary with a double thymidine block. Samples of the cells were collected at scheduled time points after the release of the block. It was found with immunoblot analysis that the protein expression of cyclin E and D, fluctuated periodically. They both began to increase in G, phase,reached the peak in S phase and declined gradually in G, phase. The protein expression of cyclin-dependent kinase P34cdk2 showed no periodical changes- The antiproliferation effect of retinoic acid or arotinoidethylester on HL-60cells was manifested by a block in Go/G1 of most of the cells and resulted in a marked decrease of the protein expression of cyclin E and D1 and no significant change of P34cdk2. These findings suggest that retinoic acid or arotinoidethylester is able to suppress the proliferation of HL-cells or to induce their differentiation.
基金Guangdong Medical Scientific Research Foundation,Guangdong Provincial Health Commission,China(2018A256 to XZ)from Guangdong Provincial Natural Scientific Foundation(2018A03030739 to JW and XZ)the Key Fostering Program of the Scientific Foundation of Guangdong Medical University,China(2019006 to JW).
文摘The BLU gene coding for zinc finger,MYND-type containing 10(ZMYND10)protein is mapped on chromosomal region 3p21.It is frequently lost in some kinds of cancers due to hypermethylation on its promoter region and identified as a tumour suppressor gene.The underlying mechanisms for BLU-mediated tumor suppression remain unclear.BLU has been reported to disturb cell cycle progression.The present study aims at examining whether ZMYND10 prevents progression of the cell cycle by targeting to repressive histone marks and downregulating the level of cyclins.Proteins structurally similar with ZMYND10 have been shown to recognize DNA sequence upstream of coding portion of the gene encoding cell cycle regulators.Enzymes,notably demethylases modifying the lysine residues are over-expressed line oncoproteins,and targeted in anti-cancer therapy.BLU was re-expressed in H1299 and HepG2 cells.The level of cyclin D1,cyclin B1 and trimethylate lysine 9 on histone 3(H3K9me3)and the binding of BLU with SIN3A(a component of the co-repressor)were detected.Cell cycle profile was measured.The evolutionary relationship between ZMYND10 and other ZMYND proteins was analysed by phylogenetic tree construction.We found that BLU expression induced G1 arrest in H1299 cells,and induced G1/G2 arrest in HepG2 cells.Cell cycle arrest was correlated with reduced activities and levels of cyclins;cyclin D1 was downregulated in H1299 cells;Both cyclin B1 and D1 were downregulated in HepG2 cells;and that BLU was associated with SIN3A.In both cell lines,the expression of H3K9me3 was induced.BLU was clustered with histone methyltransferase SMYD3 and SMYD1 on the same clade of the deduced phylogenetic tree.The results thus suggested that ZMYND10 encoded by BLU inhibited cyclins activity to prevent cell cycle progression through interaction with repressors and histone repressive marks to block the expression of genes coding for cyclins.
基金Supported by Natural Science Foundation of Guangxi Zhuang Autonomous Region,China,No.2023GXNSFAA026070 and No.2018GXNSFAA281071.
文摘BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.
文摘The cyclin-dependent kinase inhibitor p21( waf1/cip1/sdi1) is an important negative regulator in control of cell cycle. Its functions of inhibiting cancer cell growth and its effects on expression of Gl phase cyclins and related CDKs are a worthy topic for study. The plasmid expressing p2l with high level was transformed to human breast cancer cells, and the expression of p2l in cells was enhanced, then the cell growth rate, anchorage-independent growth and tu-morigenecity were tested, at the same time the expression levels of cyclinD1, CDK4,
