Exome hits demystified: The next frontier

Ithal, Dhruva; Sukumaran, Salil K.; Bhattacharjee, Debanjan; Vemula, Alekhya; Nadella, Ravi Kumar; Mahadevan, Jayant; Sud, Reeteka; Viswanath, Biju; Purushottam, Meera; Jain, Sanjeev

doi:10.1016/j.ajp.2021.102640

Cited by 6 publications

(4 citation statements)

References 288 publications

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“…29,34 It has been reported that RhoA is crucial in activating the Wnt signaling pathway. 35,36 Initially, the interaction between ARHGEF40 and RhoA was examined. As the commercially available antibodies of ARHGER40 were not suitable for co-IP, we performed endogenous co-IP by using RhoA antibody instead.…”

Section: Discussionmentioning

confidence: 99%

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ARHGEF40 promotes non‐small cell lung cancer proliferation and invasion via the AKT‐Wnt axis by binding to RhoA

Zhang

Jiang

et al. 2022

Molecular Carcinogenesis

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Rho guanine nucleotide exchange factor 40 (ARHGEF40) is a member of the Dbl-family of guanine nucleotide factor proteins. However, its expression pattern and biological function in malignant tumors, notably in nonsmall cell lung cancer (NSCLC) are currently unknown. The present study demonstrated that ARHGEF40 was highly expressed in NSCLC specimens and that its expression was significantly associated with advanced TNM stage (p < 0.001), lymph node metastasis (p = 0.002), and poor prognosis (p = 0.0056). In addition, ARHGEF40 accelerated nuclear translocation of the key component β-catenin and increased the expression levels of the Wnt signaling pathway targets c-myc, cyclin D1 and MMP7. Moreover, it promoted lung cancer cell proliferation and invasion in vitro and in vivo. To elucidate the underlying molecular mechanism, the current study demonstrated that ARHGEF40 could induce activation of the Wnt signaling pathway by increasing the phosphorylation levels of AKT and GSK3β via interaction with RhoA. Moreover, the Dbl homology (DH)-pleckstrin homology (PH) domain of ARHGEF40 was responsible for this interaction. Its deletion abolished the binding, which blocked the activation of the Wnt signaling. Taken together, the data indicated that ARHGEF40 promoted the malignant phenotype of lung cancer cells by activating the AKT-Wnt axis. This was achieved by its interaction with RhoA via the DH-PH domain.ARHGEF40 may serve as a novel target for NSCLC treatment.

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Section: Discussionmentioning

confidence: 99%

“…RhoA may also be involved in modulating the PI3K‐AKT signaling pathway 29,34 . It has been reported that RhoA is crucial in activating the Wnt signaling pathway 35,36 . Initially, the interaction between ARHGEF40 and RhoA was examined.…”

Section: Discussionmentioning

confidence: 99%

ARHGEF40 promotes non‐small cell lung cancer proliferation and invasion via the AKT‐Wnt axis by binding to RhoA

Zhang

Jiang

et al. 2022

Molecular Carcinogenesis

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“…Bipolar disorder (BD) is a severe disabling psychiatric illness with a genetic basis, and neurodevelopmental origins [Gandal et al, 2018]. Many of the identified genes in BD risk are implicated in neurodevelopmental processes and variations in brain morphology [Mühleisen et al, 2018; Ganesh et al, 2019; Dai et al, 2020; Ithal et al, 2021]. Multiple studies have documented abnormalities in brain structure in BD [Magioncalda and Martino, 2021] including smaller brain size, reduced cortical gray and white matter [Ching et al, 2020], cortical thinning [Hibar et al, 2018], and decreased interneurons in the cerebral cortex and hippocampus [Harrison et al, 2020].…”

Section: Introductionmentioning

confidence: 99%

Abnormalities in migration of neural precursor cells in familial bipolar disorder

Sukumaran

Paul

Guttal³

et al. 2021

Preprint

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Cellular migration is a ubiquitous feature of development that brings brain cells into appropriate spatial relationships. Cortical thinning has been reported in post-mortem brain samples of patients with bipolar disorder (BD). It could be that defective cellular migration during brain development is one of the contributing mechanisms in BD pathogenesis, leading to abnormalities reported at post-mortem, and during brain imaging. To probe the role of cellular migration in BD, we conducted time-lapse analysis of migration of neural precursor cells (NPCs) previously generated in our laboratory. Two NPC lines (B1 and B2) and one control line (C1) were used for the cell migration experiments. Time-lapse images were recorded every 15 min, for 15 hours, and analysed for speed and direction of cellular migration. Abnormalities in cellular migration was a common feature observed in both patient-derived NPCs. Consequently, we investigated underlying mechanistic irregularities in B1 and B2 lines that may contribute to the observed phenotype. To this end, transcriptional changes were compared between the patient-derived cells with the control line. Additionally, we examined exonic variations in genes related to cellular migration or motility. Our analysis showed downregulation of multiple genes that are all part of the EGF/ERBB signaling pathway. Collective dysregulation may be producing the defective cellular phenotype. These cellular migration abnormalities may be linked to structural changes in the brain reported in bipolar disorder.

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“…43 Mutations in this gene were found to be the cause of incomplete epilepsy with pericentral spikes (PEPS), a new mendelian idiopathic epilepsy. 44 PiRNA and siRNA are destabilized in the truancy of Hen1/Pimet, and sncRNA silencing activities are compromised. 45 Notably, under normal laboratory conditions, Hen1mutant flies do not show increased lethality or sterility, but do show increased memory delinquency, brain vacuolization, neurodegeneration, and an abridged generation.…”

mentioning

confidence: 99%

The art of onconeuroepitranscriptomics

Anurogo

2022

JKKI

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Exome hits demystified: The next frontier

Cited by 6 publications

References 288 publications

ARHGEF40 promotes non‐small cell lung cancer proliferation and invasion via the AKT‐Wnt axis by binding to RhoA

ARHGEF40 promotes non‐small cell lung cancer proliferation and invasion via the AKT‐Wnt axis by binding to RhoA

Abnormalities in migration of neural precursor cells in familial bipolar disorder

The art of onconeuroepitranscriptomics

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