scholarly journals Prognostic significance of PI3K/AKT/ mTOR signaling pathway members in clear cell renal cell carcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9261 ◽  
Author(s):  
Demin Fan ◽  
Qiang Liu ◽  
Fei Wu ◽  
Na Liu ◽  
Hongyi Qu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Protein Expression ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Clear Cell ◽  
Prognostic Significance ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Expression Levels ◽  
Prognostic Analysis

Background Renal cell carcinoma (RCC) is a fatal disease, in which the PI3K/AKT/mTOR signaling pathway serves an important role in the tumorigenesis. Previous studies have reported the prognostic significance of PI3K/AKT/mTOR signaling pathway members in RCC; however, there is insufficient evidence to date to confirm this. Thus, the present study aimed to systematically investigate the prognostic roles of multiple PI3K/AKT/mTOR signaling proteins in clear cell RCC (ccRCC) using online large-scale databases. Methods The mRNA expression profiles of PI3K/AKT/mTOR signaling pathway proteins PTEN, PIK3CA, PIK3CB, PIK3CD, PIK3CG, AKT1, AKT2, AKT3 and mTOR were investigated using the Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine databases, and the protein expression levels of PI3K, AKT and mTOR were detected using western blotting (WB) analysis. In addition, the correlation between mRNA or protein expression levels and the prognostic significance was analyzed using the Kaplan-Meier (K-M) plotter (n = 530), the Human Protein Atlas (HPA; n = 528) and The Cancer Protein Atlas (TCPA; n = 445) databases. Results The GEPIA revealed that the mRNA expression of major PI3K/AKT/mTOR pathway members, including PTEN, PIK3CA, PIK3CB, AKT1, AKT2 and AKT3, were negatively correlated with ccRCC stages (P < 0.05), though most of their mRNA and protein expression levels were notsignificantly different between ccRCC and normal tissues using GEPIA, Oncomine and WB analyses (P < 0.05). Meanwhile, using the K-M plotter and HPA prognostic analysis, it was found that the mRNA expression levels of the majority of the PI3K/AKT/mTOR signaling pathway members, including PTEN, PIK3CA, PIK3CB, PIK3CG, AKT3 and mTOR were positively correlated with overall survival (OS), whereas PIK3CD mRNA expression was negatively correlated with OS (P < 0.05). Furthermore, TCPA prognostic analysis observed that several of the key molecules of the PI3K/AKT/mTOR signaling pathway [PTEN, p-AKT (S473) and p-mTOR (S2448)] were also positively correlated with OS in patients with ccRCC (P < 0.05). In conclusion, the present study suggested that several members of the PI3K/AKT/mTOR signaling pathway, especially PTEN, may be favorable prognostic factors in ccRCC, which indicated that the PI3K/AKT/mTOR signaling pathway may be implicated in ccRCC initiation and progression.

Xihuang Pill inhibits the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway

2021 ◽  
Author(s):  
Huanfang Fan ◽  
Dehui Li ◽  
Na Guo ◽  
Chunxia Sun ◽  
Jingfei Dong ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Breast Tissue ◽  
Precancerous Lesions ◽  
Precancerous Lesion ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Vegf Mrna ◽  
Expression Levels ◽  
Pten Mrna

Abstract Objective. To study the inhibitory effect of Xihuang Pill on the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway, and to explore the effect of Xihuang Pill in preventing and treating breast cancer. Method. Establishment of a rat model of breast precancerous lesion with DMBA combined estrogen and progesterone sequential induction for 10 weeks. Xihuang Pill was administered by gavage continuously for 4 weeks. Take rat breast tissue and stain with hematoxylin- eosin (HE). The pathomorphological changes were observed with light microscope; TUNEL staining to detect cell apoptosis in breast tissue; Western blot was used to detect the protein expression of P-PI3K, P-AKT (S473), P-AKT (T308), PTEN, P-Tuberin/TSC2, P-Tuberin (p-S939), p-mTOR, P-4E-BP1 in breast tissues. The qRT-PCR was used to detect the gene expression of PTEN mRNA and VEGF mRNA. Immunohistochemistry was used to detect the protein expression of P-S6, p-p70s6k and VEGF. Result. Compared with the disease model group, the low, middle and high dose Xihuang Pill groups could significantly reduce the degree of breast pathology, and the number of apoptosis of breast precancerous lesions cells increased with the increase of Xihuang Pill dose; The expression levels of P-PI3K, P-AKT (S473), P-AKT (T308), p-mTOR, P-4E-BP1, p-S6, p-p70S6K, VEGF protein and VEGF mRNA dropped with the increase of Xihuang Pill dose. The expression levels of PTEN, P-Tuberin/TSC2, P-Tuberin (p-S939) protein and PTEN mRNA elevated with the increase of Xihuang Pill dose. Conclusion. Xihuang Pill can promote the apoptosis of breast precancerous lesion cells and reduce the proliferation of vascular endothelial cells, and then inhibit the progression of breast precancerous lesions. Its mechanism probably associated with the regulation of PI3K/AKT/mTOR pathway related gene protein expression.

scholarly journals Xihuang Pill Inhibits The Development of DMBA Combined With Oestrogen- And Progesterone-Induced Precancerous Breast lesions In Rats By The PI3K/AKT/mTOR Signaling Pathway

2021 ◽  
Author(s):  
De-hui Li ◽  
Huan-fang Fan ◽  
Na Guo ◽  
Chun-xia Sun ◽  
Jing-fei Dong ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Breast Tissue ◽  
Breast Lesion ◽  
Mtor Signaling ◽  
Breast Lesions ◽  
Mtor Signaling Pathway ◽  
Vegf Mrna ◽  
Expression Levels ◽  
Pten Mrna

Abstract Background:To study the inhibitory effect of Xihuang pill on the development of DMBA combined with oestrogen- and progesterone-induced breast precancerous lesions in rats by the PI3K/AKT/mTOR signaling pathway and to explore the effect of Xihuang pill in preventing and treating breast cancer. Method: Establishment of a rat model of precancerous breast lesions with DMBA combined with oestrogen and progesterone sequential induction for 10 weeks. Xihuang pill was administered continuously by gavage for 4 weeks. Rat breast tissue was stained with haematoxylin-eosin (HE). The pathomorphological changes were observed with a light microscope. TUNEL staining was used to detect cell apoptosis in breast tissue. Western blotting was used to detect the protein expression of P-PI3K, P-AKT (S473), P-AKT (T308), PTEN, P-tuberin/TSC2, P-tuberin (p-S939), p-mTOR, and P-4E-BP1 in breast tissues. qRT-PCR was used to detect the gene expression of PTEN mRNA and VEGF mRNA. Immunohistochemistry was used to detect the protein expression of P-S6, p-p70s6k and VEGF.Result:Compared with the disease model group, the low-, middle- and high-dose Xihuang pill groups could significantly reduce the degree of breast pathology, and the number of apoptotic precancerous breast lesion cells increased with increasing Xihuang pill dose. The expression levels of P-PI3K, P-AKT (S473), P-AKT (T308), p-mTOR, P-4E-BP1, p-S6, p-p70S6K, VEGF protein and VEGF mRNA dropped with increasing Xihuang pill dose. The expression levels of PTEN, P-tuberin/TSC2, P-tuberin (p-S939) protein and PTEN mRNA increased with increasing Xihuang pill dose. Conclusion:Xihuang pill can promote the apoptosis of precancerous breast lesion cells, reduce the proliferation of vascular endothelial cells, and then inhibit the progression of precancerous breast lesions. Its mechanism is probably associated with the regulation of the PI3K/AKT/mTOR pathway related protein expression.

scholarly journals LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway

2018 ◽  
Vol 48 (1) ◽  
pp. 371-384 ◽  
Author(s):  
Guanghua Liu ◽  
Xin Zhao ◽  
Jingmin Zhou ◽  
Xiangming Cheng ◽  
Zixing Ye ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Clear Cell ◽  
Mtor Signaling ◽  
Metastasis Suppressor ◽  
Mtor Signaling Pathway

Background/Aims: Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression. Methods: RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance. The underlying mechanisms of TP73-AS1 in ccRCC were analyzed through in vitro functional assays. Results: We found TP73-AS1 was upregulated in 40 ccRCC tissues compared with adjacent normal renal tissues and increased TP73-AS1 was correlated to aggressive clinicopathologic features and unfavorable prognosis. Knockdown of TP73-AS1 suppressed cell proliferation, invasion and induced cell apoptosis. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Knockdown of KISS1 partly reversed TP73-AS1 knockdown-induced inhibition of cell proliferation and promotion of apoptosis. We further determined that TP73-AS1 knockdown activated PI3K/Akt/mTOR signaling pathway, while overexpression of TP73-AS1 induced inhibition of PI3K/Akt/mTOR pathway and these effects could be partly abolished by overexpression of KISS1. Conclusion: In conclusion, we identified that TP73-AS1 as an oncogenic lncRNA in the development of ccRCC and a potential target for human renal carcinoma treatment.

scholarly journals Methylation of Hypothalamic Tsc1-mTOR Signaling in Regulation of Obesity and Obesity Resistance

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yanli Wang ◽  
Sijun Diao ◽  
Maoqing Hu ◽  
Lin Zhang
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Promoter Methylation ◽  
Gene Promoter ◽  
Chow Group ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Expression Levels ◽  
Tsc1 Gene ◽  
Obesity Susceptibility

The Tsc1-mTOR signaling pathway is often related to obesity, and epigenetic modification may lead to expression changes of obesity-related gene. Therefore, we aim to investigate the methylation of the Tsc1-mTOR signaling pathway in regulation of obesity susceptibility. Wistar rats were fed a normal diet or a high-fat diet to develop animal models. Protein and mRNA expression levels of Tsc1-mTOR signaling in the hypothalamus were determined by Western blot and quantitative real-time PCR. Methylation of Tsc1 gene promoter was detected by bisulfite genomic sequence. Both mRNA and protein expression levels of Tsc1 in DIO group hypothalamus were lower; mTOR and its downstream targets S6K1, 4EBP1, and S6 protein expression levels were higher than those of the DIO-R group and the chow group. The Tsc1 gene promoter methylation rate in the hypothalamus was 92.05 ± 3.07 % in the DIO group, 87.27 ± 1.91 % in the DIO-R group, and 88.18 % ± 3.20 % in the chow group, respectively, with significantly higher levels in the DIO group. Both the expression levels of Tsc1 gene promoter methylation and Tsc1-mTOR signaling pathway in the hypothalamus of DIO rats and DIO-R rats are different. These findings may shed light on the potential mechanism for the differentiation of obesity susceptibility.

Sign in / Sign up

Export Citation Format

Share Document