Lower mRNA and Protein Expression Levels of LC3 and Beclin1, Markers of Autophagy, were Correlated with Progression of Renal Clear Cell Carcinoma

Deng, Qian; Wang, Zhenlong; Wang, Lei; Zhang, Liandong; Xiang, Xiaolong; Wang, Ziming; Chong, Tie

doi:10.1093/jjco/hyt160

Cited by 33 publications

(28 citation statements)

References 25 publications

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“…LC3 is another important molecule for autophagy as a constituent of the autophagosome membrane [24]. LC3 alone or together with Beclin-1 is often used as the marker of autophagy [25]. The enhanced expression of Beclin-1 and LC3 has been observed in brain cells after focal ischemia [22].…”

Section: Discussionmentioning

confidence: 99%

Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

Zhao

Huang

Chen

et al. 2016

IJMS

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Elevated homocysteine (Hcy) levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG). Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO). Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive) and hardly in astrocytes (GFAP-positive). 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA). Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

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Section: Discussionmentioning

confidence: 99%

Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

Zhao

Huang

Chen

et al. 2016

IJMS

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“…p62 acts as a receptor or adaptor for autophagic degradation of ubiquitinated proteins, the upregulation of p62 is commonly detected in human tumors and contributes dire ctly to tumorigenesis (8). Thus, LC3, Beclin 1 and p62 were considered as autophagy markers in many studies (9,10).…”

Section: Introductionmentioning

confidence: 99%

BAMBI overexpression together with β-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-β/Smad2/3 pathway

Wang

et al. 2017

Oncology Reports

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Abstract. Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis. The BMP and activin receptor membrane bound inhibitor (BAMBI) has been identified as a hallmark of NSCLC and β-sitosterol possesses antitumor potentiality. This study explores the effect of BAMBI overexpression and β-sitosterol in the context of NSCLC. The results revealed that the transfection of pcDNA-BAMBI and β-sitosterol treatment significantly reduced the levels of autophagy markers light chain 3 (LC3) II and Beclin 1, whereas the levels of LC3 I and p62 were promoted. The reduced punctate accumulations of GFP-LC3 were detected in pcDNA-BAMBI and β-sitosterol groups, especially in pcDNA-BAMBI + β-sitosterol group. BAMBI overexpression and β-sitosterol induced G0/G1 cell cycle arrest and inhibted cell proliferation in A549 cells. In addition, the levels of transforming growth factor-β (TGF-β)/p-Smad2/3/c-Myc pathway proteins were decreased. The TGF-β overexpression further confirmed that BAMBI overexpression and β-sitosterol treatment suppre ssed autohagy and viability of A549 cells was through TGF-β/Smad2/3/c-Myc pathway. Finally, the tumor growth was suppressed in NSCLC xenografts, and the inhibitory effect was stronger under treatment of pcDNA-BAMBI together with β-sitosterol. These results indicate that BAMBI overexpression and β-sitosterol may serve as novel targets for the treatment of NSCLC. IntroductionLung cancer is the leading cause of deaths with the most rapidly increasing incidence worldwide. Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis (1). More than half of lung carcinomas are detected in a progressed or already metastasized state with a 5-year survival, for lacking of characteristic early symptoms (2). The general therapy treating the majority of patients is chemotherapy, which often induces resistance (3). It is necessary to develop novel therapeutic approaches to better understand the lung cancer progression.Autophagy is a fundamental cellular homeostatic process that cells use to degrade and recycle cellular proteins (4). This process can be induced in response to either intracellular or extracellular factors, such as hypoxia, low cellular energy state and organelle damage (5). The microtubule-associated protein 1 light chain 3 (LC3), functions as a structural component in the formation of autophagosomes. The conversion of the cytosolic form of LC3 (LC3 I) to lipidated form (LC3 II) indicates autophagosome formation (6). Beclin 1, is required for the initiation and in the process of autophagosome formation (7). p62 acts as a receptor or adaptor for autophagic degradation of ubiquitinated proteins, the upregulation of p62 is commonly detected in human tumors and contributes dire ctly to tumorigenesis (8). Thus, LC3, Beclin 1 and p62 were considered as autophagy markers in many studies (9,10).Transforming growth factor-β (TGF-β) has a crucial role in homeostasis, fibrosis angiogenesis, carcinogenesis and d...

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“…Autophagy is a process of self-digestion by a cell through the action of enzymes originating within its lysosome of the same cell (3). Autophagy is often induced under conditions of stress that could also lead to cell death (4)(5)(6). Abnormal regulation of autophagy is closely associated with the incidence and development of tumors; thus, autophagic cell death may be considered a novel target for cancer treatment (6).…”

Section: Introductionmentioning

confidence: 99%

Effect of beclin 1 expression on the biological behavior and chemotherapy sensitivity of cervical cancer cells

et al. 2016

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Abstract. The present study aimed to evaluate the effect of the expression of the autophagic gene beclin 1 on the biological behavior and chemotherapy sensitivity towards Taxol ® of cervical cancer HeLa cells. A beclin 1 expression vector was constructed and tranfected into HeLa cells. Reverse transcription-polymerase chain reaction and western blotting were used to detect the expression of beclin 1. Cell proliferation was detected based on the growth curve of the cells. The effect of beclin 1 expression on cell apoptosis was analyzed using Hoechst 33258 staining, which enabled to observe the morphology of apoptotic cells. Apoptosis-associated proteins were measured by western blot assay. The sensitivity of HeLa cells to Taxol ® was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Beclin 1 expression at the messenger RNA and protein levels was elevated following transfection of the beclin 1 expression plasmid (P<0.05). Hoechst 33258 staining revealed that the apoptosis rate of the transfected HeLa cells was significantly higher than that of normal HeLa cells. The expression of caspase-3 was increased in the transfected cells, and beclin 1 transfection increased B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax):Bcl-2 ratio, resulting in Bax activation and Bcl-2 suppression (P<0.05). Chemotherapy sensitivity analysis demonstrated that the half maximal inhibitory concentration values of Taxol ® of the transfection, non-transfection and mock-vehicle groups were 30.4, 118.0 and 125.5 µg/ml, respectively. Beclin 1 inhibited proliferation and increased apoptosis of HeLa cells, and also increased the chemosensitivity of these cells to Taxol ® . The present results confirmed that beclin 1 is a favorable prognostic biomarker for cervical cancer treatment, and may serve to identify particular patients for individual therapy.

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Lower mRNA and Protein Expression Levels of LC3 and Beclin1, Markers of Autophagy, were Correlated with Progression of Renal Clear Cell Carcinoma

Cited by 33 publications

References 25 publications

Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

BAMBI overexpression together with β-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-β/Smad2/3 pathway

Effect of beclin 1 expression on the biological behavior and chemotherapy sensitivity of cervical cancer cells

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