Regulator of G protein signaling 20 enhances cancer cell aggregation, migration, invasion and adhesion

Yang, Lei; Lee, Mei Ki; Leung, Man Hon Manton; Wong, Yung Hou

doi:10.1016/j.cellsig.2016.07.017

Cited by 36 publications

(32 citation statements)

References 55 publications

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“…High expression of RGS20 indicated the progression and poor survival of triple-negative breast cancer (33). RGS20 facilitated cell aggregation, invasion and the expression of vimentin, but decreased the expression of E-cadherin (34). By gain-of-function approaches, we revealed similar results.…”

Section: Discussionsupporting

confidence: 54%

lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR‑365/RGS20 in oral squamous cell carcinoma

Huang

He²,

Wei

2018

Oncol Rep

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Long non-coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the function and mechanism of lncRNA NEAT1 in oral squamous cell carcinoma (OSCC) are unclear. In the present study, NEAT1 was significantly upregulated in OSCC cells and tissues. High expression of NEAT1 was correlated with advanced TNM stage and poor survival of patients. Using bioinformatics prediction and experimental analysis, we determined that NEAT1 could negatively regulate the expression of miR-365. The expression of miR-365 was decreased in OSCC tissues and inversely correlated with NEAT1 in tumors. Functionally, knockdown of NEAT1 significantly inhibited cell proliferation and invasion and induced cell cycle arrest at the G0/G1 phase and apoptosis, whereas inhibition of miR-365 abolished the suppressive effect of NEAT1 knockdown on cellular processes. RGS20, a direct target of miR-365, could reverse the tumor suppressive role of miR-365 mimic by enhancing cell viability and motility. Moreover, the protein levels of RGS20, cyclin D1, E-cadherin, N-cadherin and vimentin could be regulated by the NEAT1/miR-365 axis. NEAT1 silencing also inhibited tumor growth in vivo. Collectively, we revealed that the NEAT1/miR-365/RGS20 axis may be a novel mechanism or therapeutic strategy for OSCC treatment.

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Section: Discussionsupporting

confidence: 54%

lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR‑365/RGS20 in oral squamous cell carcinoma

Huang

He²,

Wei

2018

Oncol Rep

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“…Because of its increased expression and significant changes in cellular metabolism, PKM2 has been identified as a biomarker for tissue damage such as acute kidney injury [18]. PKM2 can regulate gene transcription MEK5 by phosphorylating STAT3, which in turn activates numerous transcriptional factors to regulate cell proliferation, differentiation, migration, and survival [11,12,19]. PKM2 greatly promotes tumorous angiogenesis through enhancing the endothelial cell migration and extracellular matrix attachment [20].…”

Section: Introductionmentioning

confidence: 99%

Pyruvate Kinase M2 Increases Angiogenesis, Neurogenesis, and Functional Recovery Mediated by Upregulation of STAT3 and Focal Adhesion Kinase Activities After Ischemic Stroke in Adult Mice

et al. 2018

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Ischemic stroke remains a serious threat to human life. Generation of neuronal and vascular cells is an endogenous regenerative mechanism in the adult brain, which may contribute to tissue repair after stroke. However, the regenerative activity is typically insufficient for significant therapeutic effects after brain injuries. Pyruvate kinase isoform M2 (PKM2) is a key regulator for energy metabolism. PKM2 also has nonmetabolic roles involving regulations of gene expression, cell proliferation, and migration in cancer cells as well as noncancerous cells. In a focal ischemic stroke mouse model, recombinant PKM2 (rPKM2) administration (160 ng/kg, intranasal delivery) at 1 h after stroke showed the significant effect of a reduced infarct volume of more the 60%. Delayed treatment of rPKM2, however, lost the acute neuroprotective effect. We then tested a novel hypothesis that delayed treatment of PKM2 might show proregenerative effects for long-term functional recovery and this chronic action could be mediated by its downstream STAT3 signaling. rPKM2 (160 ng/kg) was delivered to the brain using noninvasive intranasal administration 24 h after the stroke and repeated every other day. Western blot analysis revealed that, 7 days after the stroke, the levels of PKM2 and phosphorylated STAT3 and the expression of angiogenic factors VEGF, Ang-1, and Tie-2 in the peri-infarct region were significantly increased in the rPKM2 treatment group compared with those of the stroke vehicle group. To label proliferating cells, 5-bromo-2'-deoxyuridine (BrdU, 50 mg/kg, i.p.) was injected every day starting 3 days after stroke. At 14 days after stroke, immunohistochemistry showed that rPKM2 increased cell homing of doublecortin (DCX)-positive neuroblasts to the ischemic cortex. In neural progenitor cell (NPC) cultures, rPKM2 (0.4-4 nM) increased the expression of integrin β1 and the activation/phosphorylation of focal adhesion kinase (FAK). A mediator role of FAK in PKM2-promoted cell migration was verified in FAK-knockout fibroblast cultures. In the peri-infarct region of the brain, increased numbers of Glut-1/BrdU and NeuN/BrdU double-positive cells indicated enhanced angiogenesis and neurogenesis, respectively, compared to stroke vehicle mice. Using Laser Doppler imaging, we observed better recovery of the local blood flow in the peri-infarct region of rPKM2-treated mice 14 days after stroke. Meanwhile, rPKM2 improved the sensorimotor functional recovery measured by the adhesive removal test. Inhibiting the STAT3 phosphorylation/activation by the STAT3 inhibitor, BP-1-102 (3 mg/kg/day, o.g.), abolished all beneficial effects of rPKM2 in the stroke mice. Taken together, this investigation provides the first evidence demonstrating that early treatment of rPKM2 shows an acute neuroprotective effect against ischemic brain damage, whereas delayed rPKM2 treatment promotes regenerative activities in the poststroke brain leading to better functional recovery. The underlying mechanism involves activation of the STAT3 and FAK signals in the pos...

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“…Smoking and substance dependence James et al, 2009;Yoon et al, 2012;Zhang et al, 2012;Hayes and Roman, 2016 RGS19 Heart, lung, brain, and Garzon et al, 2004;Kohara et al, 2008;Yang et al, 2016a RGS5 variants and neurologic disorders, such as schizophrenia and bipolar disorder (Campbell et al, 2008b;Smith et al, 2009), its role is best defined in the vasculature. In this work, RGS5 is expressed in arterial smooth muscle cells, and its expression is correlated with protection from hypertension and atherosclerosis (Holobotovskyy et al, 2013;Cheng et al, 2015;Daniel et al, 2016).…”

Section: Rgs17 Brainmentioning

confidence: 99%

“…RGS20, also known as RGSZ1 and Ret RGS, selectively interacts with Gaz and Gai2 subunits (Wang et al, 1998(Wang et al, , 2002. The RGS20 transcript is highly expressed in human caudate nucleus and temporal lobe (Wang et al, 1998), and RGS20 splice variants are detectable in the eye (Barker et al, 2001;Yang et al, 2016a). Loss of RGS20 in mice leads to enhanced m-opioid-induced analgesia and tolerance to morphine (Garzon et al, 2004).…”

Section: The Rz Familymentioning

confidence: 99%

“…Loss of RGS20 in mice leads to enhanced m-opioid-induced analgesia and tolerance to morphine (Garzon et al, 2004). Outside the brain, RGS20 is found at significantly high levels in melanoma and metastatic breast cancer cells (Yang et al, 2016a). Furthermore, expression of RGS20 in HeLa, breast adenocarcinoma MDA-MB-231, non-small cell lung carcinoma H1299, and A549 cells results in enhanced cell aggregation, migration, invasion, and adhesion, suggesting a role for RGS20 in tumor metastasis (Yang et al, 2016a).…”

Section: The Rz Familymentioning

confidence: 99%

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Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease

et al. 2018

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Regulators of G protein signaling (RGS) proteins modulate the physiologic actions of many neurotransmitters, hormones, and other signaling molecules. Human RGS proteins comprise a family of 20 canonical proteins that bind directly to G protein-coupled receptors/G protein complexes to limit the lifetime of their signaling events, which regulate all aspects of cell and organ physiology. Genetic variations account for diverse human traits and individual predispositions to disease. RGS proteins contribute to many complex polygenic human traits and pathologies such as hypertension, atherosclerosis, schizophrenia, depression, addiction, cancers, and many others. Recent analysis indicates that most human diseases are due to extremely rare genetic variants. In this study, we summarize physiologic roles for RGS proteins and links to human diseases/traits and report rare variants found within each human RGS protein exome sequence derived from global population studies. Each RGS sequence is analyzed using recently described bioinformatics and proteomic tools for measures of missense tolerance ratio paired with combined annotation-dependent depletion scores, and protein post-translational modification (PTM) alignment cluster analysis. We highlight selected variants within the well-studied RGS domain that likely disrupt RGS protein functions and provide comprehensive variant and PTM data for each RGS protein for future study. We propose that rare variants in functionally sensitive regions of RGS proteins confer profound change-of-function phenotypes that may contribute, in newly appreciated ways, to complex human diseases and/or traits. This information provides investigators with a valuable database to explore variation in RGS protein function, and for targeting RGS proteins as future therapeutic targets.

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Regulator of G protein signaling 20 enhances cancer cell aggregation, migration, invasion and adhesion

Cited by 36 publications

References 55 publications

lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR‑365/RGS20 in oral squamous cell carcinoma

lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR‑365/RGS20 in oral squamous cell carcinoma

Pyruvate Kinase M2 Increases Angiogenesis, Neurogenesis, and Functional Recovery Mediated by Upregulation of STAT3 and Focal Adhesion Kinase Activities After Ischemic Stroke in Adult Mice

Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease

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