Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation

Sankpal, Umesh T.; Ingersoll, Susan B.; Ahmad, Sarfraz; Holloway, Robert W.; Bhat, Vadiraja B.; Simecka, Jerry W.; Daniel, Liz; Kariali, Ekamber; Vishwanatha, Jamboor K.; Basha, Riyaz

doi:10.1007/s13277-016-5290-9

Cited by 26 publications

(16 citation statements)

References 38 publications

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“…Regulation of FOXO3a and SP1 linked to the Stat3 signaling and involved in a number of cellular functions, such as tumorigenesis, progression, growth, and metastasis, has been shown in other studies [44, 45, 58]. The induction of FOXO3a and inhibition of SP1, and interaction between FOXO3a and SP1 have also been reported to be associated with regulation of other genes, thereby controlling cancer cell survival in other studies, this demonstrates the critical roles of these transcription factors in these processes [59-61]. For example, high expression of SP1 was observed in the ovarian cancer cells and that the SP1 inhibitor was found to enhance the response of cisplatin on growth inhibition [59].…”

Section: Discussionmentioning

confidence: 58%

“…The induction of FOXO3a and inhibition of SP1, and interaction between FOXO3a and SP1 have also been reported to be associated with regulation of other genes, thereby controlling cancer cell survival in other studies, this demonstrates the critical roles of these transcription factors in these processes [59-61]. For example, high expression of SP1 was observed in the ovarian cancer cells and that the SP1 inhibitor was found to enhance the response of cisplatin on growth inhibition [59]. Also, cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGF-R), stimulated FOXO3a expression and promoted its nuclear translocation, leading to induction of apoptosis and inhibition of proliferation in colorectal cancer cells [60].…”

Section: Discussionmentioning

confidence: 84%

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Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Tang

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE₂) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined. Methods: Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colorimetric 5-bromo-2-deoxyuridine (BrdU) ELISA methods, respectively. Western blot analysis and immunohistochemistry were performed to examine the phosphorylation and protein expressions of signal transducer and activator of transcription 3 (Stat3), SP1, forkhead box O3a (FOXO3a), and insulin-like growth factor (IGF)-IGF binding protein 1 (IGFBP1). The expression of IGFBP1 mRNA was measured by quantitative real time PCR (qRT-PCR). Silencing of FOXO3a and IGFBP1 were examined by siRNA procedures. Exogenously expression of SP1, FOXO3a, and IGFBP1 were carried out by transient transfection assays. The promoter activity of IGFBP1 was tested using Secrete-Pair^TM Dual Luminescence Assay Kit. A xenografted tumor model was used to further test the effect of solamargine in combining with metformin in vivo. Results: We further demonstrated that solamargine inhibited growth and induced cell cycle arrest in other NSCLC cell lines. Through mechanism-based approaches, we showed that solamargine decreased the phosphorylation of Stat3; In addition, solamargine induced FOXO3a, whereas reduced SP1 protein levels; all of which were abrogated in cells with overexpressed Stat3 gene. Interestingly, there is interaction between FOXO3a and SP1. Moreover, solamargine increased mRNA, protein expression and promoter activity of IGFBP1, which was not observed in cells with overexpressed SP1 or with silenced FOXO3a genes. Finally, ablation of IGFBP1 expression by siRNA blocked the effect of solamargine on cell growth inhibition. More importantly, there was a synergy of combination of solamargine and metformin. Similar findings were also observed in vivo. Conclusion: Our results show that solamargine increases IGFBP1 gene expression through inactivation of Stat3, followed by regulation and reciprocal interaction of FOXO3a and SP1 in vitro and in vivo. This ultimately leads to suppression of human lung cancer cell growth. Moreover, this is a synergy of solamargine in combination with metformin in this process. This study unravels a novel mechanism underlying the anti-lung cancer effects of solamargine in combination of metformin, and suggests a potential new lung cancer associated therapy.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 84%

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Tang

Zheng

et al. 2017

Cell Physiol Biochem

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“…Survivin expression is minimal in normal tissues; therefore, it has become a lead target for both as a tumor diagnostic, prognostic and for anti-cancer therapies. Mounting evidence has demonstrated that survivin takes part in the regulation of cell cycle, apoptosis, cell proliferation as well as invasion and play important roles in various tumor carcinogenesis, such as gastric cancer [7], bladder cancer [8], epithelial ovarian cancer [9].…”

Section: Introductionmentioning

confidence: 99%

LncRNA FENDRR represses proliferation, migration and invasion through suppression of survivin in cholangiocarcinoma cells

Qin

Zhou

et al. 2019

Cell Cycle

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This study was to investigate the biological function and underlying mechanisms of FENDRR in cholangiocarcinoma (CCA) cell proliferation, migration and invasion. FENDRR and survivin expression in CCA tissues or cell lines were measured by qRT-PCR. In QBC939 and HuCCTl cells, cell proliferation was detected by CCK-8, cell migration and invasion were using transwell assay. RNA pull-down and RIP assay were performed to determine whether FENDRR can combine with SETDB1 in CCA cell. The effect of SETDB1 on survivin and H3K9me1 expression in CCA cells were determined by western blotting. ChIP analysis was performed to analyze the combination of SETDB1 with survivin promoter in CCA cell. The effect of SETDB1 knockdown on survivin and H3K9me1 expression in CCA cells after transfection with FENDRR were determined by western blotting. The results showed that lncRNA FENDRR was downregulated in CCA tissues and cells, and was negatively correlated with survivin expression. Further investigation demonstrated that FENDRR represses CCA cell proliferation, migration and invasion through regulating survivin expression. FENDRR associated with SETDB1 and H3K9 to epigenetically silence survivin and then regulated cell proliferation, migration and invasion. These findings indicate an important role for FENDRR-survivin axis in CCA cell proliferation, migration and invasion, and reveal a novel epigenetic mechanism for survivin silencing. Our data indicated that FENDRR silences survivin via SETDB1-mediated H3K9 methylation, thereby represses CCA cell proliferation, migration and invasion. ARTICLE HISTORY

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“…Therefore, study of the mechanisms that regulate VEGFA is important. And the oncogenetic role of TGF‐α and survivin in ovarian cancer cells has also been confirmed …”

Section: Discussionmentioning

confidence: 83%

“…And the oncogenetic role of TGF-α and survivin in ovarian cancer cells has also been confirmed. [35][36][37]…”

Section: Discussionmentioning

confidence: 99%

CircRhoC promotes tumorigenicity and progression in ovarian cancer by functioning as a miR‐302e sponge to positively regulate VEGFA

Wang

Zong

Liu

et al. 2019

J Cellular Molecular Medi

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Ovarian cancer is a leading cause of deaths due to gynaecological malignancy. While endogenous non‐coding circular RNAs (circRNAs) in cancer have attracted attention, their roles in ovarian cancer are not known. We used qRT‐PCR to quantify expression of circRhoC in ovarian cancer tissues and normal tissues. The effects of overexpressing or destruction of circRhoC on the phenotype of ovarian cancer cells were assessed both in vitro and in vivo. Dual‐luciferase reporter assay assesses the microRNA sponge function of circRhoC. Western blotting was used to confirm the effects of circRhoC and microRNA on target gene expression. Our results showed that circRhoC was significantly up‐regulated in ovarian cancer tissues compared to normal ovarian tissues. Overexpression of circRhoC in CAOV3 ovarian cancer cell increased cell viability, migration and invasion ability; destroying circRhoC in A2780 had the opposite effects and inhibited ovarian tumour cell A2780 dissemination in the peritoneum in vivo. We confirmed circRhoC functions as a sponge for miR‐302e to positively regulate VEGFA; FISH experiments showed that circRhoC could co‐focal with miR‐302e; besides, overexpression of miR‐302e reversed the ability of circRhoC to positively regulate VEGFA, and what's more, RIP assay showed that circRhoC could directly bind with VEGFA; besides, VEGFA expression level in ovarian cancer tissues was positively associated with circRhoC expression. In conclusion, the oncogenic effect of RhoC in ovarian cancer is at least in part due to circRhoC, which functions not only as a miR‐302e sponge to positively regulate VEGFA protein expression, but may also directly bind and modulate VEGFA expression.

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Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation

Cited by 26 publications

References 38 publications

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

LncRNA FENDRR represses proliferation, migration and invasion through suppression of survivin in cholangiocarcinoma cells

CircRhoC promotes tumorigenicity and progression in ovarian cancer by functioning as a miR‐302e sponge to positively regulate VEGFA

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