New insight into NANOG: A novel therapeutic target for ovarian cancer (OC)

Iyer, Mahalaxmi; Devi, Subramaniam Mohana; Jayaramayya, Kaavya; Narayanasamy, Arul; Vellingiri, Balachandar; Santhy, K. S.

doi:10.1016/j.ejphar.2019.03.003

Cited by 34 publications

(24 citation statements)

References 66 publications

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“…Ovarian cancer is a prevalent gynecological malignancy, which severely threatens women's health (19). Ovarian cancer occurs in women with a prevalence ~15,000 per 100,000 individuals worldwide (20). Due to a lack of specific symptoms in the early stages, 60-70% of patients with ovarian cancer are diagnosed at an advanced stage, and their 5-year survival rate is ~40% (21,22).…”

Section: Introductionmentioning

confidence: 99%

PTEN/AKT/mTOR signaling mediates anticancer effects of epigallocatechin‑3‑gallate in ovarian cancer

Qin

Wang

et al. 2020

Oncol Rep

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Epigallocatechin-3-gallate (EGCG), a polyphenol present in green tea, exhibits anticancer effects in various types of cancer. A number of studies have focused on the effects of EGCG on lung cancer, but not ovarian cancer. Previous reports have implicated that EGCG suppressed ovarian cancer cell proliferation and induced apoptosis, but its potential anticancer mechanisms and signaling pathways remain unclear. Thus, it is necessary to determine the anti-ovarian cancer effects of EGCG and explore the underlying mechanisms. In the present study, EGCG exerted stronger proliferation inhibition on SKOV3 cells compared with A549 cells and induced apoptosis in SKOV3 cells, as well as upregulated PTEN expression and downregulated the expression of phosphoinositide-dependent kinase-1 (PDK1), phosphor (p)-AKT and p-mTOR. These effects were reversed by the PTEN inhibitor VO-Ohpic trihydrate. The results of the mouse xenograft experiment demonstrated that 50 mg/kg EGCG exhibited increased tumor growth inhibition compared with 5 mg/kg paclitaxel. In addition, PTEN expression was upregulated, whereas the expression levels of PDK1, p-AKT and p-mTOR were downregulated in the EGCG treatment group compared with those in untreated mice in vivo. In conclusion, the results of the present study provided a new underlying mechanism of the effect of EGCG on ovarian cancer and may lead to the development of EGCG as a candidate drug for ovarian cancer therapy.

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Section: Introductionmentioning

confidence: 99%

PTEN/AKT/mTOR signaling mediates anticancer effects of epigallocatechin‑3‑gallate in ovarian cancer

Qin

Wang

et al. 2020

Oncol Rep

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“…Ovarian cancer (OC) has a very poor prognosis because of delayed diagnosis in most of the patients and resistance to some cytotoxic drugs. A major obstacle that jeopardizes OC chemotherapeutic treatment is multidrug resistance (MDR) [1]. A remarkable number of studies have revealed the importance of Sp1 in this regard, as it regulates potent drug targets as well as promoter genes that are overexpressed in OC [40,61].…”

Section: Sp1 As a Therapeutic Target In Ocmentioning

confidence: 99%

“…Recently Saha et al, has pointed out that the biology of reprogramming in the framework of replicative age of the cells needs more appropriate stimulating agents such as a more reliable TF to reduce the epigenetic stress caused during reprogramming process [112]. The durability of the cancer cells was strong due to the presence of stem cell-like property in them which is known as CSCs [1]. Thus, recent functional study has mentioned that targeting the CSCs in the cancer cells using either molecular medicine or TFs-induced reprogramming of iPSCs would provide a positive effect in blocking the progression and invasion of the cancer cells [113].…”

Section: Influence Of Sp1 On Cellular Reprogrammingmentioning

confidence: 99%

“…Ovarian cancer (OC) has been identified as the deadliest multidrug resistant cancer among females, especially at their perimenopausal stage [1]. Reports suggest that OC is the second most…”

Section: Introductionmentioning

confidence: 99%

“…Presently, there are no early-stage treatment options for OC since the early symptoms cannot be comprehended. Due to high prevalence and the continuously rising incidence, OC poses a major threat to personal health as well as the health care system [1]. Despite ongoing efforts to detect OC, specific diagnostic biomarkers are yet to be identified [4].…”

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confidence: 99%

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Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice

Vellingiri

Iyer

Subramaniam

et al. 2020

IJMS

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Ovarian cancer (OC) is one of the deadliest cancers among women contributing to high risk of mortality, mainly owing to delayed detection. There is no specific biomarker for its detection in early stages. However, recent findings show that over-expression of specificity protein 1 (Sp1) is involved in many OC cases. The ubiquitous transcription of Sp1 apparently mediates the maintenance of normal and cancerous biological processes such as cell growth, differentiation, angiogenesis, apoptosis, cellular reprogramming and tumorigenesis. Sp1 exerts its effects on cellular genes containing putative GC-rich Sp1-binding site in their promoters. A better understanding of the mechanisms underlying Sp1 transcription factor (TF) regulation and functions in OC tumorigenesis could help identify novel prognostic markers, to target cancer stem cells (CSCs) by following cellular reprogramming and enable the development of novel therapies for future generations. In this review, we address the structure, function, and biology of Sp1 in normal and cancer cells, underpinning the involvement of Sp1 in OC tumorigenesis. In addition, we have highlighted the influence of Sp1 TF in cellular reprogramming of iPSCs and how it plays a role in controlling CSCs. This review highlights the drugs targeting Sp1 and their action on cancer cells. In conclusion, we predict that research in this direction will be highly beneficial for OC treatment, and chemotherapeutic drugs targeting Sp1 will emerge as a promising therapy for OC. common reproductive cancer among women in India [2]. Although OC is a single disease, its clinical pathway is mostly intercalated by other tumor types having different prognosis stages, morphologies, and molecular and epigenetic backgrounds [3]. Presently, there are no early-stage treatment options for OC since the early symptoms cannot be comprehended. Due to high prevalence and the continuously rising incidence, OC poses a major threat to personal health as well as the health care system [1]. Despite ongoing efforts to detect OC, specific diagnostic biomarkers are yet to be identified [4]. It is evident that transcription factors (TFs) play a pivotal role in the regulation of cellular functions, including cell activation, repression, and alteration of gene expression. Any dysfunctional activation or inactivation of TFs may result in cellular induction of tumorigenesis [4]. Mutations in cancer is caused due to changes in various proteins functions and transcriptions factors which are controlling the protein, thus changing the phenotypes in human [5]. Bookmarking of mitosis constitutes a mechanism that transmits transcriptional patterns by cell division. Bookmarking factors, comprising a subset of TFs, and multiple histone modifications retained in mitotic chromatin facilitate reactivation of transcription in the early G1 phase [6]. It is possible that Sp1 phosphorylation may change its interaction with other transcription factors [7]. Specificity protein 1 (Sp1) is one such ubiquitous and multifunctional TF from the Sp/Kru...

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Cancer‐testis antigen ACRBP expression and serum immunoreactivity in ovarian cancer: Its association with prognosis

Lin

Nong

Luo

et al. 2021

Immunity Inflam & Disease

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Introduction: Cancer testis (CT) antigens are attractive targets for cancer immunotherapy because of their expression restriction and immunogenicity. The acrosin binding protein (ACRBP) is a member of CT antigens. This study aimed to evaluate ACRBP expression and immunogenicity in ovarian cancer (OC). Methods:The expression level of ACRBP in OC tissues, normal ovarian tissues, and cell lines was detected via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. We determined the levels of ACRBP antigen and antibody in serum samples collected from patients with OC and healthy donors using enzyme-linked immunosorbent assays (ELISA), the level of ACRBP in cell-cultured medium was also tested. Results: ACRBP mRNA and protein expressions were upregulated in OC tissues relative to normal tissue, especially highly expressed in epithelial ovarian cancer (EOC). Moreover, ACRBP expression was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and chemosensitivity. Serological analysis showed that anti-ACRBP antibody was detected in the sera of 16 of the 56 (28.5%) patients with OC but not in healthy donors. The area under the receiver operating characteristic curve for ACRBP antibody was 0.802 (95% confidence interval [CI]: 0.708-0.876), and the sensitivity and specificity for ACRBP antibody was 85.71% and 55.0%, respectively. Kaplan-Meier analysis revealed that the overall survival (OS) and disease-free survival (DFS) in OC patients with high ACRBP expression were significantly lower than those with low expression (p = 0.040, p = 0.021). However, ACRBP antibody level was not associated with prognosis. Conclusion:ACRBP expression was upregulated in OC tissues and induced humoral immune response in patients with OC, suggesting that ACRBP is a potential prognostic biomarker and a target of tumor immunotherapy for OC.

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New insight into NANOG: A novel therapeutic target for ovarian cancer (OC)

Cited by 34 publications

References 66 publications

PTEN/AKT/mTOR signaling mediates anticancer effects of epigallocatechin‑3‑gallate in ovarian cancer

PTEN/AKT/mTOR signaling mediates anticancer effects of epigallocatechin‑3‑gallate in ovarian cancer

Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice

Cancer‐testis antigen ACRBP expression and serum immunoreactivity in ovarian cancer: Its association with prognosis

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