Systematic expression alteration analysis of master reprogramming factor OCT4 and its three pseudogenes in human cancer and their prognostic outcomes

Saha, Subbroto Kumar; Jeong, Yeojin; Cho, Sungha; Cho, Ssang-Goo

doi:10.1038/s41598-018-33094-7

Cited by 28 publications

(32 citation statements)

References 68 publications

(89 reference statements)

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“…Conversely, consistent with our previous data, OCT4A and OCT4Bv transcripts were undetectable or expressed at very low levels in MCF7, a non-aggressive cancer cell line (Fig. 2b) [16], suggesting that the expression of these OCT4 transcripts is positively correlated with the aggressiveness of breast and endometrial cancer cells, which is inconsistent with a previous bioinformatics analysis [24].…”

Section: Expression Of Oct4-transcript Variants In Malignant and Non-supporting

confidence: 55%

“…These results renew the discussion surrounding a critical role for OCT4A or other OCT4 variants in human somatic cancers and germ-cell tumours. To our knowledge, variant-specific expression of OCT4 transcripts could not be assessed using currently available high-throughput databases [18,24]; therefore, in the present study, we explored the potential of multiple OCT4 transcript variants to act as prognostic biomarkers in human somatic cancers.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma

et al. 2020

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Background: Octamer-binding transcription factor 4A (OCT4A) is essential for cell pluripotency and reprogramming both in humans and mice. To date, however, the function of human OCT4 in somatic and/or tumour tissues is largely unknown. Methods: RT-PCR was used to identify full-length splice forms of OCT4 transcripts in normal and cancer cells. A FLAG-tagged OCT4 genomic transgene was used to identify OCT4-positive cancer cells. A potential role for OCT4 in somatic cancer cells was examined by cell ablation of OCT4-positive cells using promoter-driven diphtheria toxin A. OCT4 and secreted phosphoprotein 1 (SPP1) transcripts in early-stage lung adenocarcinoma tumours were analysed and compared with pathohistological features. Results: The results show that, unlike in murine cells, OCT4A and OCT4B variants are transcribed in both human cancer cells and in adult tissues such as lung, kidney, uterus, breast, and eye. We found that OCT4A and SPP1C are co-expressed in highly aggressive human breast, endometrial, and lung adenocarcinoma cell lines, but not in mesothelial tumour cell lines. Ablation of OCT4-positive cells in lung adenocarcinoma cells significantly decreased cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinoma tumours. Conclusions: Co-expression of OCT4 and SPP1 may correlate with cancer aggressiveness, and the OCT4A/SPP1C axis may help identify early-stage high-risk patients with lung adenocarcinoma. Contrary to the case in mice, our data strongly suggest a critical role for OCT4A and SPP1C in the development and progression of human epithelial cancers.

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Section: Expression Of Oct4-transcript Variants In Malignant and Non-supporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma

et al. 2020

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“…Embryonic stem cells transcription factors such as octamer-binding transcription factor 4 (Oct4) and sex determining region Y-box 2 (Sox2) are thought to be involved in the regulatory of stem cells and contribute to tumorigenesis and progression of human breast cancer [26] . While other studies reported that overexpression of OCT4 could inhibit the metastasis of breast cancer cells [27] . Besides, Sox2 is considered to be one of the important stem cell transcription factors.…”

Section: Effects Of Arsenic Trioxide and Tetrandrine On The Morphologmentioning

confidence: 94%

Effect of tetrandrine combined with arsenic trioxide on stem cells of triple negative breast cancer

Guo

Fan

et al. 2019

Preprint

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Background Although the triple negative breast cancer is sensitive to chemotherapy, breast cancer stem cells (BCSCs) is the origin of tumor chemotherapy resistance, tumor recurrence and tumor invasion and metastasis. This study aims to examine the effect of tetrandrine combine with arsenic trioxide on BCSCs and potential mechanism of anti- triple negative breast cancer metastasis. Methods We cultured the triple negative breast cancer cell MDA-MB-231 and induced BCSCs sphere formation by serum-free medium for 5 days. In the MDA-MB-231 cell and MDA-MB-231 stem cell, we compared the ratio of CD44+/CD24- and sorted stem cells by flow cytometry, the expression of Oct4 and Sox2mRNA were by rt-PCR, invasion ability were by Transwell assay. We subsequently measured the effect of tetrandrine combine with arsenic trioxide on BCSCs proliferation by CCK8 method. The stem cell morphology observation was by trypan blue staining. Stem cell cycle and apoptosis were evaluated by flow cytometry. Western Blot was used to measure the protein levels of Hedgehog, Notch1 and PTEN signaling of BCSCs. Results The ratio of CD44+/CD24- in MDA-MB-231 stem cells was 95.0%, while MDA-MB-231 cell was 89.3%. The invasion number of MDA-MB-231 stem cell was significantly higher than that of MDA-MB-231 cells (p<0.01). Furthermore, we demonstrated that tetrandrine and arsenic trioxide could inhibit the BCSCs proliferation. Tetrandrine combine with arsenic trioxide could significantly promote the apoptosis (p<0.01) and increase the percentage of G0/G1 phase and decrease the G2/M phase (p<0.01) of BCSCs. Compared with the control group, arsenic trioxide, tetrandrine and the combined group could significantly reduce the expression of GLI1 and SMO and increase the expression of PTEN protein (P<0.05). Conclusions These findings revealed that tetrandrine combined with arsenic trioxide could suppress the proliferation and induce apoptosis of BCSCs by decreased Gli and SMO expression and increased PTEN expression. Targeting BCSCs treatment, this study provides potential therapeutic drugs against triple negative breast cancer metastasis.

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“…Recently it has been reported that iPSC technology is been evolving as a promising therapy to treat various diseases such as cancer, neurological disorders, cardiovascular diseases and so on [111]. 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].…”

Section: Influence Of Sp1 On Cellular Reprogrammingmentioning

confidence: 99%

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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Systematic expression alteration analysis of master reprogramming factor OCT4 and its three pseudogenes in human cancer and their prognostic outcomes

Cited by 28 publications

References 68 publications

Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma

Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma

Effect of tetrandrine combined with arsenic trioxide on stem cells of triple negative breast cancer

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

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