Downregulation of cell division cycle 25 homolog C reduces the radiosensitivity and proliferation activity of esophageal squamous cell carcinoma

Yin, Yachao; Dou, Xiaoyan; Duan, Shimiao; Zhang, Lei; Xu, Quanjing; Li, Hongwei; Li, Duojie

doi:10.1016/j.gene.2016.05.025

Cited by 5 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These MT1-MMP-mediated functions may explain the enhanced invasion observed in the ovarian cancer cell lines with decreased TIMP-2 expression after siRNA treatment. Enhanced proliferation in response to TIMP-2 suppression may result due to enhancement in the expression of cell cycle analogues CDC25B and CDC25C, which may drive cells through G2 and M phases [56]. However, in the FT282 cell line, knockdown of TIMP-2 may only enhance the M2 phase of the cell cycle through CDC25B.…”

Section: Discussionmentioning

confidence: 99%

TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells

et al. 2020

View full text Add to dashboard Cite

Background The metzincin family of metalloproteinases and the tissue inhibitors of metalloproteinases (TIMPs) are essential proteins required for biological processes during cancer progression. This study aimed to determine the role of TIMP-2 in ovarian cancer progression and chemoresistance by reducing TIMP-2 expression in vitro in Fallopian tube secretory epithelial (FT282) and ovarian cancer (JHOS2 and OVCAR4) cell lines. Methods FT282, JHOS2 and OVCAR4 cells were transiently transfected with either single or pooled TIMP-2 siRNAs. The expression of different genes after TIMP-2 knock down (T2-KD) or in response to chemotherapy was determined at the mRNA level by quantitative real time PCR (qRT-PCR) and at the protein level by immunofluorescence. Sensitivity of the cell lines in response to chemotherapy after TIMP-2 knock down was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-Ethynyl-2′-deoxyuridine (EdU) assays. Cell invasion in response to TIMP-2 knockdown was determined by xCELLigence. Results Sixty to 90 % knock down of TIMP-2 expression was confirmed in FT282, OVCAR4 and JHOS2 cell lines at the mRNA and protein levels. TIMP-2 knock down did not change the mRNA expression of TIMP-1 or TIMP-3. However, a significant downregulation of MMP-2 in T2-KD cells occurred at both the protein and activation levels, compared to Control (Cont; scrambled siRNA) and Parental cells (P, transfection reagent only). In contrast, membrane bound MT1-MMP protein levels were significantly upregulated in T2-KD compared to Cont and P cells. T2-KD cells exhibited enhanced proliferation and increased sensitivity to cisplatin and paclitaxel treatments. Enhanced invasion was observed in the T2-KD-JOSH2 and OVCAR4 cells but not in T2-KD-FT282 cells. Treatment with cisplatin or paclitaxel significantly elevated the expression of TIMP-2 in Cont cells but not in T2-KD cells, consistent with significantly elevated expression of chemoresistance and CSC markers and activation of STAT3. Furthermore, a potent inhibitor of STAT3 activation, Momelotinib, suppressed chemotherapy-induced activation of P-STAT3 in OVCAR4 cells with concomitant reductions in the expression of chemoresistance genes and CSC markers. Conclusions The above results suggest that TIMP-2 may have a novel role in ovarian cancer proliferation, invasion and chemoresistance.

show abstract

Section: Discussionmentioning

confidence: 99%

TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Not only tissue‐specific genes but also genes related to proliferation and differentiation were affected. On day 2, hBMSCs cultured under SMG exhibited down‐regulation of the genes related to cell cycle, such as MCM5 , CCNA2, CCNB1 , CDK1 , E2F1 , CDC25B and CDC25C . It has been reported that microgravity changes the distribution of the cell cycle phase in many mammalian cells, such as primitive human haematopoietic progenitor cells and endothelial cells .…”

Section: Discussionmentioning

confidence: 99%

“…On day 2, hBMSCs cultured under SMG exhibited down-regulation of the genes related to cell cycle, such as MCM5, CCNA2, CCNB1, CDK1, E2F1, CDC25B and CDC25C. [16][17][18][19][20][21][22] It has been reported that microgravity changes the distribution of the cell cycle phase in many mammalian cells, such as primitive human haematopoietic progenitor cells 23 and endothelial cells. 24 In addition, several studies have shown that microgravity has a major effect on the cytoskeleton, 25,26 and changes in cytoskeleton may play an important role in the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Effects of simulated microgravity on the expression profiles of RNA during osteogenic differentiation of human bone marrow mesenchymal stem cells

Zhang

Chen

et al. 2018

Cell Proliferation

View full text Add to dashboard Cite

Objectives: Exposure to microgravity induces many adaptive and pathological changes in human bone marrow mesenchymal stem cells (hBMSCs). However, the underlying mechanisms of these changes are poorly understood. We revealed the gene expression patterns of hBMSCs under normal ground (NG) and simulated microgravity (SMG), which showed an interpretation for these changes by gene regulation and signal pathways analysis. Materials and methods:In this study, hBMSCs were osteogenically induced for 0, 2, 7 and 14 days under normal ground gravity and simulated microgravity, followed by analysis of the differences in transcriptome expression during osteogenic differentiation by RNA sequencing and some experimental verification for these results. Results:The results indicated that 837, 399 and 894 differentially expressed genes (DEGs) were identified in 2, 7 and 14 days samples, respectively, out of which 13 genes were selected for qRT-PCR analysis to confirm the RNA-sequencing results.After analysis, we found that proliferation was inhibited in the early stage of induction. In the middle stage, osteogenic differentiation was inhibited, whereas adipogenic differentiation benefited from SMG. Moreover, SMG resulted in the up-regulation of genes specific for tumorigenesis in the later stage. Conclusion:Our data revealed that SMG inhibits the proliferation and inhibits the differentiation towards osteoblasts but promotes adipogenesis. SMG also selects highly tumorigenic cells for survival under prolonged SMG.

show abstract

“…After knocking down the expression of CDC25C in human esophageal squamous cell carcinoma cell lines, the cells were found to decrease sensitivity to radiotherapy and inhibited cell proliferation activity. Therefore, CDC25C is considered to be a potential biomarker for radiation therapy [168]. By testing the expression of CDC25C antibody in the serum of patients with tumor, it can help to their diagnosis and treatment.…”

Section: Cdc25c Expression Level and Clinical Outcomementioning

confidence: 99%

The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review

et al. 2020

View full text Add to dashboard Cite

One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related proteins gives tumor cells their invasive, metastatic, drug-resistance, and anti-apoptotic abilities. Recently, an increasing number of cell cycle-associated proteins have become the candidate biomarkers for early diagnosis of malignant tumors and potential targets for cancer therapies. As an important cell cycle regulatory protein, Cell Division Cycle 25C (CDC25C) participates in regulating G2/M progression and in mediating DNA damage repair. CDC25C is a cyclin of the specific phosphatase family that activates the cyclin B1/CDK1 complex in cells for entering mitosis and regulates G2/M progression and plays an important role in checkpoint protein regulation in case of DNA damage, which can ensure accurate DNA information transmission to the daughter cells. The regulation of CDC25C in the cell cycle is affected by multiple signaling pathways, such as cyclin B1/CDK1, PLK1/Aurora A, ATR/CHK1, ATM/CHK2, CHK2/ERK, Wee1/Myt1, p53/Pin1, and ASK1/JNK-/38. Recently, it has evident that changes in the expression of CDC25C are closely related to tumorigenesis and tumor development and can be used as a potential target for cancer treatment. This review summarizes the role of CDC25C phosphatase in regulating cell cycle. Based on the role of CDC25 family proteins in the development of tumors, it will become a hot target for a new generation of cancer treatments.

show abstract

Downregulation of cell division cycle 25 homolog C reduces the radiosensitivity and proliferation activity of esophageal squamous cell carcinoma

Cited by 5 publications

References 19 publications

TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells

TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells

Effects of simulated microgravity on the expression profiles of RNA during osteogenic differentiation of human bone marrow mesenchymal stem cells

The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review

Contact Info

Product

Resources

About