scholarly journals PTEN Activation by DNA Damage Induces Protective Autophagy in Response to Cucurbitacin B in Hepatocellular Carcinoma Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Yanan Niu ◽  
Wen Sun ◽  
Jin-Jian Lu ◽  
Dik-Lung Ma ◽  
Chung-Hang Leung ◽  
...  
Keyword(s):  
Dna Damage ◽  
Carcinoma Cells ◽  
Caspase Activation ◽  
Phosphatase And Tensin Homolog ◽  
Cucurbitacin B ◽  
Tensin Homolog ◽  
Phosphorylated Akt ◽  
Protein Expressions ◽  
Ros Formation ◽  
Induced Apoptosis

Cucurbitacin B (Cuc B), a natural product, induced both protective autophagy and DNA damage mediated by ROS while the detailed mechanisms remain unclear. This study explored the mechanism of Cuc B-induced DNA damage and autophagy. Cuc B decreased cell viability in concentration- and time-dependent manners. Cuc B caused long comet tails and increased expression of γ-H2AX, phosphorylation of ATM/ATR, and Chk1/Chk2. Cuc B induced autophagy as evidenced by monodansylcadaverine (MDC) staining, increased expression of LC3II, phosphorylated ULK1, and decreased expression of phosphorylated AKT, mTOR. Cuc B induced apoptosis mediated by Bcl-2 family proteins and caspase activation. Furthermore, Cuc B induced ROS formation, which was inhibited by N-acetyl-L-cysteine (NAC). NAC pretreatment dramatically reversed Cuc B-induced DNA damage, autophagy, and apoptosis. Cuc B-induced apoptosis was reversed by NAC but enhanced by 3-methyladenine (3-MA), chloroquine (CQ), and silencing phosphatase and tensin homolog (PTEN). 3-MA and CQ showed no effect on Cuc B-induced DNA damage. In addition, Cuc B increased PTEN phosphorylation and silence PTEN restored Cuc B-induced autophagic protein expressions without affecting DNA damage. In summary, Cuc B induced DNA damage, apoptosis, and protective autophagy mediated by ROS. PTEN activation in response to DNA damage bridged DNA damage and prosurvival autophagy.

scholarly journals MiR-718 mediates the indirect interaction between lncRNA SEMA3B-AS1 and PTEN to regulate the proliferation of hepatocellular carcinoma cells

2019 ◽  
Vol 51 (10) ◽  
pp. 500-505 ◽  
Author(s):  
Yuchuan Zhong ◽  
Yan Li ◽  
Tao Song ◽  
Dapeng Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Gastric Cardia Adenocarcinoma ◽  
Indirect Interaction ◽  
Poor Survival ◽  
Hepatocellular Carcinoma Cells ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
B Virus ◽  
Hcc Cells

It has been reported that SEMA3B-AS1 is a tumor-suppressive lncRNA in gastric cardia adenocarcinoma. We explored the possible involvement of SEMA3B-AS1 in hepatocellular carcinoma (HCC). We found that SEMA3B-AS1 was downregulated in HCC tissues compared with noncancer tissues and was not affected by hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In addition, SEMA3B-AS1 expression was not affect by cancer development, and low SEMA3B-AS1 levels were closely correlated with poor survival. SEMA3B-AS1 in HCC tissues was inversely correlated with microRNA (miR)-718 and positively correlated with PTEN. In HCC cells, SEMA3B-AS1 overexpression resulted in upregulated, while miR-718 overexpression resulted in downregulated phosphatase and tensin homolog (PTEN) expression. In addition, miR-718 overexpression attenuated the effects of SEMA3B-AS1 overexpression. SEMA3B-AS1 and PTEN overexpression resulted in a reduced proliferation rate of HCC cells, while miR-718 overexpression resulted in an increased rate. In addition, miR-718 overexpression attenuated the effects of SEMA3B-AS1 overexpression. Therefore, miR-718 may mediate the indirect interaction between lncRNA SEMA3B-AS1 and PTEN to regulate the proliferation of hepatocellular carcinoma cells.

LINC00893 inhibits papillary thyroid cancer by suppressing AKT pathway via stabilizing PTEN

2020 ◽  
pp. 1-10
Author(s):  
Shujing Li ◽  
Yanyan Zhang ◽  
Jian Dong ◽  
Ruihuan Li ◽  
Bo Yu ◽  
...  
Keyword(s):  
Akt Pathway ◽  
Phosphatase And Tensin Homolog ◽  
Fused In Sarcoma ◽  
Tensin Homolog ◽  
Phosphorylated Akt ◽  
Pten Mrna ◽  
Non Coding Rnas ◽  
And Migration ◽  
Fus Protein ◽  
Proliferation And Migration

Long non-coding RNAs (lncRNAs) are important to the occurrence and advancement of human cancers. We found through GEPIA that LINC00893 was lowly expressed in thyroid carcinoma (THCA) tissues, whereas the specific functions of LINC00893 has never been reported in PTC. In the current study, we confirmed that LINC00893 was expressed at a low level in PTC cells. Through gain-of-function assays, we determined that LINC00893 overexpression abrogated proliferation and migration abilities of PTC cells. Through signal transduction reporter array we found that LINC00893 potentially modulated the signals of phosphatase and tensin homolog (PTEN)/AKT pathway. In addition, overexpression of LINC00893 increased the expression of PTEN but reduced the levels of phosphorylated AKT in PTC. Additionally, mechanism assays unveiled that LINC00893 stabilized PTEN mRNA via recruiting Fused in sarcoma (FUS) protein. Finally, rescue assays demonstrated that LINC00893 hampered the proliferation and migration of PTC cells via PTEN/AKT pathway. Together, our study first clarified that LINC00893 functions as a tumor suppressor in PTC by blocking AKT pathway through PTEN upregulation.

Induction of DNA Damage-Inducible Gene GADD45β Contributes to Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma Cells

2010 ◽  
Vol 70 (22) ◽  
pp. 9309-9318 ◽  
Author(s):  
Da-Liang Ou ◽  
Ying-Chun Shen ◽  
Sung-Liang Yu ◽  
Kuen-Feng Chen ◽  
Pei-Yen Yeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Damage ◽  
Carcinoma Cells ◽  
Hepatocellular Carcinoma Cells ◽  
Induced Apoptosis ◽  
Inducible Gene

MAPK regulation and caspase activation are required in DMNQ S-52 induced apoptosis in Lewis lung carcinoma cells

2006 ◽  
Vol 233 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Soo Jin Lee ◽  
Hiroaki Sakurai ◽  
Keiichi Koizumi ◽  
Gyu Yong Song ◽  
Yong Soo Bae ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Carcinoma Cells ◽  
Lewis Lung ◽  
Caspase Activation ◽  
Lung Carcinoma Cells ◽  
Induced Apoptosis ◽  
Lewis Lung Carcinoma Cells

scholarly journals Ordering of ceramide formation, caspase activation, and mitochondrial changes during CD95- and DNA damage–induced apoptosis

1999 ◽  
Vol 103 (7) ◽  
pp. 971-978 ◽  
Author(s):  
Annemiek D. Tepper ◽  
Evert de Vries ◽  
Wim J. van Blitterswijk ◽  
Jannie Borst
Keyword(s):  
Dna Damage ◽  
Caspase Activation ◽  
Induced Apoptosis

scholarly journals The Protective Effect of Early Hypothermia on PTEN Phosphorylation Correlates with Free Radical Inhibition in Rat Stroke

2009 ◽  
Vol 29 (9) ◽  
pp. 1589-1600 ◽  
Author(s):  
Sang Mi Lee ◽  
Heng Zhao ◽  
Carolina M Maier ◽  
Gary K Steinberg
Keyword(s):  
Protective Effect ◽  
Artery Occlusion ◽  
Akt Pathway ◽  
Moderate Hypothermia ◽  
Ischemic Damage ◽  
Protective Mechanisms ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Phosphorylated Akt ◽  
Transient Focal Ischemia

We recently showed that intraischemic moderate hypothermia (30°C) reduces ischemic damage through the Akt pathway after permanent distal middle cerebral artery occlusion in rats. The only Akt pathway component preserved by hypothermia is phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (p-PTEN), which suggests that p-PTEN may have a central role in neuroprotection. Reactive oxygen species (ROS) are critically involved in mediating ischemic damage after stroke by interacting with signaling molecules, including Akt, PTEN, and δ-protein kinase C (PKC). We investigated the protective mechanisms of moderate hypothermia on these signaling proteins after transient focal ischemia in rats. Early moderate hypothermia (3h) was administered 15 mins before reperfusion, and delayed moderate hypothermia (3h) was applied 15 mins after reperfusion. Our results indicate that early hypothermia reduced infarction, whereas delayed hypothermia did not. However, both early and delayed hypothermia maintained levels of Mn-SOD (superoxide dismutase) and phosphorylated Akt and blocked δ-PKC cleavage, suggesting that these factors may not be critical to the protection of hypothermia. Nevertheless, early hypothermia preserved p-PTEN levels after reperfusion, whereas delayed hypothermia did not. Furthermore, ROS inhibition maintained levels of p-PTEN after stroke. Together, these findings suggest that phosphorylation levels of PTEN are closely associated with the protective effect of early hypothermia against stroke.

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