https://transhumanist.ru/index.php?action=history&feed=atom&title=DLC1 2026-04-09T13:52:31Z История изменений этой страницы в вики MediaWiki 1.43.6 https://transhumanist.ru/index.php?title=DLC1&diff=6384&oldid=prev 2021-05-12T15:27:41Z

<p>Новая страница: «Rho GTPase-activating protein 7 (Deleted in liver cancer 1 protein) (DLC-1) (HP protein) (Rho-type GTPase-activating protein 7) (START domain-containing protein 1...»</p> <p><b>Новая страница</b></p><div>Rho GTPase-activating protein 7 (Deleted in liver cancer 1 protein) (DLC-1) (HP protein) (Rho-type GTPase-activating protein 7) (START domain-containing protein 12) (StARD12) (StAR-related lipid transfer protein 12) [ARHGAP7] [KIAA1723] [STARD12]<br /> <br /> ==Publications==<br /> <br /> {{medline-entry<br /> |title=Resveratrol promotes oxidative stress to drive [[DLC1]] mediated cellular senescence in cancer cells.<br /> |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29964052<br /> |abstract=Induction of cellular senescence represents a novel strategy to inhibit aberrant proliferation of cancer cells. Resveratrol is gaining attention for its cancer preventive and suppressive properties. Tumor suppressor gene [[DLC1]] is shown to induce apoptosis, suppress migration and invasion in various cancer cells. However, the function of [[DLC1]] in cancer cellular senescence is unclear. This study was designed to investigate the biological role of [[DLC1]] in resveratrol induced cancer cellular senescence. Our results showed that resveratrol inhibited proliferation of cancer cell lines (MCF-7, MDA-[[MB]]-231 and H1299) and induced senescence along with increase of SA-β-gal activity and regulation of senescence-associated molecular markers p38MAPK, p-p38MAPK, p27, p21, Rb and p-Rb protein. The underlying mechanism was that resveratrol induced mitochondrial dysfunction with reduction of mitochondrial membrane potential, down-regulation of MT-ND1, MT-ND6 and ATPase8 in transcript level and down-regulation of [[PGC]]-1α in protein level to result in ROS production. With ROS elevation, resveratrol decreased [[DNMT1]] and increased [[DLC1]] expression significantly. However, after ROS scavenger NAC was added to the cancer cells treated by resveratrol, [[DNMT1]], [[DLC1]] and senescence-associated molecular markers were reversed. This reveals that resveratrol induced cancer cellular senescence through [[DLC1]] in a ROS-dependent manner. Silencing [[DLC1]] markedly attenuated SA-β-gal activity and p38MAPK, p27 and p21 protein levels, and increased Rb expression, indicating that resveratrol promoted senescence via targeting [[DLC1]]. Moreover, [[DLC1]] promoted senescence through FoxO3a/NF-κB signaling mediated by [[SIRT1]] after resveratrol treatment. Finally, resveratrol increased ROS production to induce DNA damage with p-CHK1 up-regulation and result in cancer cellular senescence. This is the first time to investigate resveratrol induced cancer cellular senescence by primarily targeting [[DLC1]]. Induction of cellular senescence by resveratrol may represent a novel anticancer mechanism.<br /> |mesh-terms=* Cellular Senescence<br /> * DNA Damage<br /> * GTPase-Activating Proteins<br /> * Genes, Mitochondrial<br /> * Humans<br /> * Oxidative Stress<br /> * Reactive Oxygen Species<br /> * Resveratrol<br /> * Signal Transduction<br /> * Tumor Suppressor Proteins<br /> * p38 Mitogen-Activated Protein Kinases<br /> |keywords=* Cellular senescence<br /> * DLC1<br /> * Mitochondrial dysfunction<br /> * Reactive oxygen species<br /> * Resveratrol<br /> * SIRT1<br /> |full-text-url=https://sci-hub.do/10.1016/j.yexcr.2018.06.031<br /> }}<br /> {{medline-entry<br /> |title=Depletion of the transcriptional coactivators megakaryoblastic leukaemia 1 and 2 abolishes hepatocellular carcinoma xenograft growth by inducing oncogene-induced senescence.<br /> |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23853104<br /> |abstract=Megakaryoblastic leukaemia 1 and 2 (MKL1/2) are coactivators of the transcription factor serum response factor (SRF). Here, we provide evidence that depletion of MKL1 and 2 abolishes hepatocellular carcinoma (HCC) xenograft growth. Loss of the tumour suppressor deleted in liver cancer 1 ([[DLC1]]) and the subsequent activation of RhoA were prerequisites for MKL1/2 knockdown-mediated growth arrest. We identified oncogene-induced senescence as the molecular mechanism underlying the anti-proliferative effect of MKL1/2 knockdown. MKL1/2 depletion resulted in Ras activation, elevated p16 expression and hypophosphorylation of the retinoblastoma (Rb) protein in [[DLC1]]-deficient HCC cells. Interestingly, reconstitution of HuH7 HCC cells with [[DLC1]] also induced senescence. Evaluation of the therapeutic efficacy of MKL1/2 knockdown in vivo revealed that systemic treatment of nude mice bearing HuH7 tumour xenografts with MKL1/2 siRNAs complexed with polyethylenimine (PEI) completely abolished tumour growth. The regression of the xenografts was associated with senescence. Importantly, PEI-complexed MKL1 siRNA alone was sufficient for complete abrogation of HCC xenograft growth. Thus, MKL1/2 represent promising novel therapeutic targets for the treatment of HCCs characterized by [[DLC1]] loss. <br /> |mesh-terms=* Aging<br /> * Animals<br /> * Carcinoma, Hepatocellular<br /> * Cell Proliferation<br /> * DNA-Binding Proteins<br /> * Gene Knockdown Techniques<br /> * Heterografts<br /> * Humans<br /> * Mice<br /> * Mice, Nude<br /> * Oncogene Proteins<br /> * Oncogene Proteins, Fusion<br /> * Trans-Activators<br /> * Transcription Factors<br /> |keywords=* DLC1<br /> * MKL1<br /> * MKL2<br /> * MRTF<br /> * senescence<br /> |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799492<br /> }}</div>

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