mTOR signalling pathway - A root cause for idiopathic autism?

Ganesan, Harsha; Venkatesh, Balasubramanian; Iyer, Mahalaxmi; Venugopal, Anila; Subramaniam, Mohana Devi; Cho, Ssang-Goo; Vellingiri, Balachandar

doi:10.5483/bmbrep.2019.52.7.137

Cited by 62 publications

(48 citation statements)

References 91 publications

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“…To overcome these issues, the most promising method is to use TF induced reprogramming to iPSC because it makes the process very simpler and sturdy [110]. 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].…”

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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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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“…Separate network prediction analyses of genes in all of the modules correlated with each trait revealed both overlapping and unique canonical pathways associated with each trait, as summarized in Figure 5. Among the shared pathways are those involving regulation of eIF4 and p70S6K signaling as well as ERK/MAPK, mTOR, and androgen signaling, all of which have been implicated in ASD (7,(35)(36)(37)(38)(39)(40).…”

Section: Biological Associations With Autistic Traits In Simplex Famimentioning

confidence: 99%

Phenotypic Subtyping and Re-analyses of Existing Transcriptomic Data from Autistic Probands in Simplex Families Reveal Differentially Expressed and ASD Trait-Associated Genes

2020

Front. Neurol.

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“…Sestrin has been shown to interact with p53 and forkhead box class O (FoxO) transcription factors and mediate antioxidant regulation [12]. Activation of 5 adenosine monophosphate-activated protein kinase (AMPK) and inhibition of mTORC1 are important for cell cycle and cell lifespan [13]. Since sestrins can modulate pathways of cellular metabolism, sestrin expression seems to play an important role in prolonging life and inhibiting aging [2].…”

Section: Introductionmentioning

confidence: 99%

Sestrin2 Expression Has Regulatory Properties and Prognostic Value in Lung Cancer

Chae

Gil

Saha

et al. 2020

JPM

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Lung cancer remains the most dangerous type of cancer despite recent progress in therapeutic modalities. Development of prognostic markers and therapeutic targets is necessary to enhance lung cancer patient survival. Sestrin family genes (Sestrin1, Sestrin2, and Sestrin3) are involved in protecting cells from stress. In particular, Sestrin2, which mainly protects cells from oxidative stress and acts as a leucine sensor protein in mammalian target of rapamycin (mTOR) signaling, is thought to affect various cancers in different ways. To investigate the role of Sestrin2 expression in lung cancer cells, we knocked down Sestrin2 in A549, a non-small cell lung cancer cell line; this resulted in reduced cell proliferation, migration, sphere formation, and drug resistance, suggesting that Sestrin2 is closely related to lung cancer progression. We analyzed Sestrin2 expression in human tissue using various bioinformatic databases and confirmed higher expression of Sestrin2 in lung cancer cells than in normal lung cells using Oncomine and the Human Protein Atlas. Moreover, analyses using Prognoscan and KMplotter showed that Sestrin2 expression is negatively correlated with the survival of lung cancer patients in multiple datasets. Co-expressed gene analysis revealed Sestrin2-regulated genes and possible associated pathways. Overall, these data suggest that Sestrin2 expression has prognostic value and that it is a possible therapeutic target in lung cancer.

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mTOR signalling pathway - A root cause for idiopathic autism?

Cited by 62 publications

References 91 publications

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

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

Phenotypic Subtyping and Re-analyses of Existing Transcriptomic Data from Autistic Probands in Simplex Families Reveal Differentially Expressed and ASD Trait-Associated Genes

Sestrin2 Expression Has Regulatory Properties and Prognostic Value in Lung Cancer

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