Biological and clinical significance of the intratumour heterogeneity of PTEN protein expression and the corresponding molecular abnormalities of thePTENgene in glioblastomas

2014 ◽  
Vol 40 (6) ◽  
pp. 736-746 ◽  
Author(s):  
Miguel A. Idoate ◽  
Jose Echeveste ◽  
Ricardo Diez-Valle ◽  
Maria Dolores Lozano ◽  
José Aristu
Keyword(s):  
Protein Expression ◽  
Clinical Significance ◽  
Pten Protein ◽  
Molecular Abnormalities ◽  
Intratumour Heterogeneity

scholarly journals MicroRNA-1297 suppressed the Akt/GSK3β signaling pathway and stimulated neural apoptosis in an in vivo sevoflurane exposure model

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052098210
Author(s):  
Quan Wang ◽  
Jingcong Luo ◽  
Ruiqiang Sun ◽  
Jia Liu
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
In Vitro Model ◽  
Nervous System Development ◽  
Exposure Model ◽  
Control Group ◽  
Pten Protein ◽  
Vitro Model

Objective Common inhalation anesthetics used for clinical anesthesia (such as sevoflurane) may induce nerve cell apoptosis during central nervous system development. Furthermore, anesthetics can produce cognitive impairments, such as learning and memory impairments, that continue into adulthood. However, the precise mechanism remains largely undefined. We aimed to determine the function of microRNA-1297 (miR-1297) in sevoflurane-induced neurotoxicity. Methods Reverse transcription-polymerase chain reaction assays were used to analyze miR-1297 expression in sevoflurane-exposed mice. MTT and lactate dehydrogenase (LDH) assays were used to measure cell growth, and neuronal apoptosis was analyzed using flow cytometry. Western blot analyses were used to measure PTEN, PI3K, Akt, and GSK3β protein expression. Results In sevoflurane-exposed mice, miR-1297 expression was up-regulated compared with the control group. MiR-1297 up-regulation led to neuronal apoptosis, inhibition of cell proliferation, and increased LDH activity in the in vitro model of sevoflurane exposure. MiR-1297 up-regulation also suppressed the Akt/GSK3β signaling pathway and induced PTEN protein expression in the in vitro model. PTEN inhibition (VO-Ohpic trihydrate) reduced PTEN protein expression and decreased the effects of miR-1297 down-regulation on neuronal apoptosis in the in vitro model. Conclusion Collectively, the results indicated that miR-1297 stimulates sevoflurane-induced neurotoxicity via the Akt/GSK3β signaling pathway by regulating PTEN expression.

scholarly journals Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Wuping Yang ◽  
Kenan Zhang ◽  
Lei Li ◽  
Yawei Xu ◽  
Kaifang Ma ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Clinical Significance ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Level ◽  
Cell Renal Cell Carcinoma ◽  
Qrt Pcr

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

scholarly journals Clinical significance of Reg IV protein expression in human colorectal cancer

2010 ◽  
Vol 18 (33) ◽  
pp. 3594
Author(s):  
Sheng-Qin Zheng ◽  
Jie He ◽  
Pei-Lin Huang ◽  
Jian-Hua Wang
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Clinical Significance ◽  
Human Colorectal Cancer

scholarly journals The expression and clinical significance of PDCD4 and Her-2 in human gastric cancer

2019 ◽  
Vol 17 ◽  
pp. 205873921982823
Author(s):  
Yuelou Yang ◽  
Xiangjun Jiang ◽  
Dong Li ◽  
Feiyan Wang ◽  
Qun Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Western Blot ◽  
Clinical Significance ◽  
Normal Mucosa ◽  
Normal Tissues ◽  
Positive Rate ◽  
Her 2 ◽  
Cancer Tissues ◽  
Pdcd4 Protein

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.

scholarly journals The relevance of precision epitope mapping for accurate oncologic diagnostic based on PTEN protein expression in tumours

2017 ◽  
Vol 28 ◽  
pp. vii8-vii9
Author(s):  
J. Mingo ◽  
S. Luna ◽  
A. Gaafar ◽  
R. Ruiz ◽  
A. Carracedo ◽  
...  
Keyword(s):  
Protein Expression ◽  
Epitope Mapping ◽  
Pten Protein

Effect of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on Akt protein expression is more effective in head and neck cancer cell lineages that retain PTEN protein expression

2018 ◽  
Vol 47 (3) ◽  
pp. 253-259
Author(s):  
Flávia Sirotheau C. Pontes ◽  
Hélder A. R. Pontes ◽  
Lucas L. de Souza ◽  
Adriana S. de Jesus ◽  
Andrea M. C. Joaquim ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Protein Expression ◽  
Head And Neck ◽  
Cancer Cell ◽  
Neck Cancer ◽  
Pten Protein ◽  
Cell Lineages

Reduced PTEN Protein Expression and Its Prognostic Implications in Canine and Feline Mammary Tumors

2009 ◽  
Vol 46 (5) ◽  
pp. 860-868 ◽  
Author(s):  
L. Ressel ◽  
F. Millanta ◽  
E. Caleri ◽  
V. M. Innocenti ◽  
A. Poli
Keyword(s):  
Protein Expression ◽  
Lymphatic Vessel ◽  
Mammary Tumors ◽  
Lymphatic Vessel Invasion ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Mammary Carcinomas ◽  
Tensin Homolog ◽  
Vessel Invasion ◽  
Distant Organ

Phosphatase and tensin homolog (PTEN) belongs to the group of gatekeeper tumor suppressor genes and is involved in multiple mechanisms leading to cellular defense against neoplastic transformation and progression. Twenty-four dogs and 17 cats were submitted to a 2-year follow-up study, and clinicopathologic features were recorded and compared with immunohistochemical PTEN staining. PTEN-negative status occurred in 33% of canine and 76% of feline mammary carcinomas. In canine mammary carcinomas, there was a significant ( P < .05) correlation between loss of PTEN protein expression and simple carcinoma histotype, lymphatic vessel invasion, lymph node metastases, distant organ metastases, tumor dedifferentiation, tumor recurrence, and shorter overall survival. In feline mammary tumors, a significant correlation between loss of PTEN protein expression and lymphatic vessel invasion was found. Loss of PTEN expression could be a useful prognostic marker in canine mammary carcinomas.

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