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

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.

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

10.21203/rs.3.rs-151758/v1 ◽

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.

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

PeerJ ◽

10.7717/peerj.9261 ◽

2020 ◽

Vol 8 ◽

pp. e9261 ◽

Cited By ~ 1

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.

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

BioMed Research International ◽

10.1155/2020/8723869 ◽

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.

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Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin-Resistant Gastric Cancer SGC7901/DDP Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210528144006 ◽

2021 ◽

Vol 21 ◽

Author(s):

Dongmei Zhan ◽

Tengyang Ni ◽

Haibo Wang ◽

Mengying Lv ◽

Masataka Sunagawa ◽

...

Keyword(s):

Gastric Cancer ◽

Drug Resistance ◽

Signaling Pathway ◽

Resistance Index ◽

Mtor Signaling ◽

Control Group ◽

Human Gastric Cancer ◽

Cancer Resistance ◽

Mtor Signaling Pathway ◽

Expression Levels

Background: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreases drug resistance of cisplatin-resistant gastric cancer cells. Objective: To explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. Methods: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatin-resistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug resistance index (DRI). According to the half inhibitory concentration (IC50) value, the action concentration of the following experimental drugs was set to reduce the cytotoxicity; Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol; Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway related proteins; Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. Results: (1) Compared with the control group (We set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4μmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug resistance index DRI of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. Conclusion: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.

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T-cadherin deficiency promotes endometriosis progression through the PI3K/AKT/mTOR signaling pathway

10.21203/rs.3.rs-18041/v1 ◽

2020 ◽

Author(s):

yutao guan ◽

Fu-bin Zhang ◽

Yan-qing Huang ◽

Ling-ling Zhou ◽

Wei-feng Li ◽

...

Keyword(s):

Cell Migration ◽

Protein Expression ◽

Signaling Pathway ◽

Benign Disease ◽

Mtor Signaling ◽

Migration And Invasion ◽

Mtor Signaling Pathway ◽

Cell Migration And Invasion ◽

Female Patients ◽

Mrna And Protein Expression

Abstract Background: Endometriosis is a progressive and benign disease characterized by the presence of endometrial glands and stroma tissue outside of the uterine cavity. Though endometriosis is a benign disease, it has the characteristics of malignant tumour growth. Abnormal expression of T-cadherin is involved in the occurrence and progression of many tumours. We aimed to investigate whether T-cadherin promotes the migration and invasion of endometriosis cells through the PI3K/AKT/mTOR signaling pathway. Methods: Ectopic and eutopic endometrial samples from 62 female patients with endometriosis and endometrial samples from 51 female patients without endometriosis were collected. The immortalized endometrial stromal cell line hEM15A was cultured. Real-time RT-PCR, immunohistochemistry and Western blot were used to detect the expression of T-cadherin, phospho-PI3K/Akt/mTOR and matrix metalloproteinase 2 (MMP-2). Transfection technology was employed to upregulate T-cadherin expression. The migration and invasion abilities of hEM15A cells were measured by the transwell assay with uncoated or Matrigel-coated membranes. Results: The mRNA and protein expression of T-cadherin was significantly decresed in the ectopic tissues of the patients with endometriosis, while the mRNA and protein expression in the eutopic endometrial tissues of the same patients did not significantly differ from that in the patients without endometriosis. The migration and invasion ability and phospho-PI3K/Akt/mTOR and MMP-2 expression levels were decreased in hEM15A cells with high T-cadherin expression compared with the corresponding parameters in the normal control group. However, everolimus and BEZ235 inhibited cell migration and invasion in cells with low T-cadherin expression, and weakened overexpression of T‑cadherin significantly attenuated MMP-2 protein expression. Conclusion: Loss of T-cadherin promotes cell migration and invasion in endometriosis via the PI3K/AKT/mTOR signalling pathway.

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GPR30 Activation by 17β-Estradiol Promotes p62 Phosphorylation and Increases Estrogen Receptor α Protein Expression by Inducing Its Release from a Complex Formed with KEAP1

Journal of Personalized Medicine ◽

10.3390/jpm11090906 ◽

2021 ◽

Vol 11 (9) ◽

pp. 906

Author(s):

Chia-Lung Tsai ◽

Chiao-Yun Lin ◽

Angel Chao ◽

Yun-Shien Lee ◽

Ren-Chin Wu ◽

...

Keyword(s):

Estrogen Receptor ◽

Protein Expression ◽

Signaling Pathway ◽

Critical Role ◽

Adaptor Protein ◽

Estrogen Receptor Α ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

17Β Estradiol ◽

Esr1 Expression

Estrogens can elicit rapid cellular responses via the G-protein-coupled receptor 30 (GPR30), followed by estrogen receptor α (ERα/ESR1)-mediated genomic effects. Here, we investigated whether rapid estrogen signaling via GRP30 may affect ESR1 expression, and we examined the underlying molecular mechanisms. The exposure of human endometrial cancer cells to 17β-estradiol promoted p62 phosphorylation and increased ESR1 protein expression. However, both a GPR30 antagonist and GPR30 silencing abrogated this phenomenon. GPR30 activation by 17β-estradiol elicited the SRC/EGFR/PI3K/Akt/mTOR signaling pathway. Intriguingly, unphosphorylated p62 and ESR1 were found to form an intracellular complex with the substrate adaptor protein KEAP1. Upon phosphorylation, p62 promoted ESR1 release from the complex, to increase its protein expression. Given the critical role played by p62 in autophagy, we also examined how this process affected ESR1 expression. The activation of autophagy by everolimus decreased ESR1 by promoting p62 degradation, whereas autophagy inhibition with chloroquine increased ESR1 expression. The treatment of female C57BL/6 mice with the autophagy inhibitor hydroxychloroquine—which promotes p62 expression—increased both phosphorylated p62 and ESR1 expression in uterine epithelial cells. Collectively, our results indicate that 17β-estradiol-mediated GPR30 activation elicits the SRC/EGFR/PI3K/Akt/mTOR signaling pathway and promotes p62 phosphorylation. In turn, phosphorylated p62 increased ESR1 expression by inducing its release from complexes that included KEAP1. Our findings may lead to novel pharmacological strategies aimed at decreasing ESR1 expression in estrogen-sensitive cells.

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Astragaloside IV attenuated TGF-β1- induced epithelial-mesenchymal transition of renal tubular epithelial cells via connexin43 and Akt/mTOR signaling pathway

10.21203/rs.3.rs-1026692/v1 ◽

2021 ◽

Author(s):

Yonghong Lian ◽

Cuiqiong Li ◽

Jianchun Li ◽

Yongxiang Xie ◽

Qiancheng Liu ◽

...

Keyword(s):

Signaling Pathway ◽

Interstitial Fibrosis ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Renal Interstitial Fibrosis ◽

Mesenchymal Transition ◽

Expression Levels ◽

Protein Expressions ◽

Tgf Β1 ◽

Different Doses

Abstract INTRODUCTION: The objective of the study was to observe whether Cx43 could regulate EMT of RTECs by influencing Akt/mTOR signaling pathway, and whether ASV could inhibit the development of renal interstitial fibrosis by regulating Cx43. METHODS: Lentivirus infection was transfected into RTECs with the final concentration of 50×PFU/ cell to regulate the expression of Cx43.And RTECs were intervened by different doses of ASV. After synchronous culture of RTECs in each group,cell morphological changes were observed and the expression levels of EMT-related indicators, and the expression levels of Cx43, the protein expressions and phosphorylation levels AKT and mTOR in different groups were detected by WB. RESULTS: When the expression of Cx43 in RTECs was regulated by lentivirus infection, the degree of EMT induced by TGF‑β1 and the phosphorylation level of Akt and mTOR were changed accordingly, indicating that Akt/mTOR pathway might be a downstream molecular mechanism by which Cx43 could regulate EMT. After intervention with different doses of ASV, the expression level of Cx43 increased with obvious concentration dependence, and the expression levels of p-Akt and p- mTOR were significantly altered, suggesting that ASV could effectively increase the protein expressions of TGF‑β1-induced Cx43 in RTECs and inhibit the phosphorylation levels of Akt and mTOR. CONCLUSION: Cx43 is the main material basis of RTECs’injury, and ASV could inhibit TGF-β1 induced RTECs transdifferentiation. In-depth study of the mechanism may provide a broad application prospect for the treatment of renal interstitial fibrosis.

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Coenzyme Q10 Ameliorates Pancreatic Fibrosis via the ROS-Triggered mTOR Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/8039694 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Ran Xue ◽

Jianxin Wang ◽

Lixin Yang ◽

Xinjuan Liu ◽

Yan Gao ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Coenzyme Q10 ◽

Mtor Signaling ◽

Pancreatic Fibrosis ◽

Collagen Deposition ◽

Mtor Signaling Pathway ◽

Histological Changes ◽

Expression Levels ◽

Specific Inhibitors

Aim. Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis. Any remedies that inhibit the activation of PSCs can be potential candidates for therapeutic strategies in pancreatic fibrosis-related pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Our study is aimed at exploring the protective effect of coenzyme Q10 (CoQ10) against pancreatic fibrosis. Methods. Pancreatic fibrosis was induced by 20% L-arginine (250 mg/100 g) at 1 h intervals twice per week for 8 weeks in C57BL/6 mice. CoQ10 was administered for 4 weeks. Isolated primary PSCs from C57BL/6 mice were treated with 100 μM CoQ10 for 72 h, as well as Rosup and specific inhibitors. The effects of CoQ10 on the activation of PSCs, autophagy, collagen deposition, histological changes, and oxidative stress were analyzed by western blotting, biochemical estimations, immunofluorescence staining, and hematoxylin-eosin, Masson, and Sirius red staining, as well as with a reactive oxygen species (ROS) assay. Results. Pretreatment and posttreatment of CoQ10 decreased autophagy, activation of PSCs, oxidative stress, histological changes, and collagen deposition in the CP mouse model. In primary PSCs, expression levels of p-PI3K, p-AKT, and p-mTOR were upregulated with CoQ10. A rescue experiment using specific inhibitors of the PI3K-AKT-mTOR pathway demonstrated that the PI3K-AKT-mTOR signaling pathway was the underlying mechanism by which CoQ10 ameliorated fibrosis. With the addition of Rosup, expression levels of the autophagy biomarkers LC3 and Atg5 were elevated. Meanwhile, the levels of p-PI3K, p-AKT, and p-mTOR were lower. Conclusions. Our findings demonstrated that CoQ10 alleviates pancreatic fibrosis by the ROS-triggered PI3K/AKT/mTOR signaling pathway. CoQ10 may be a therapeutic candidate for antifibrotic methods.

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SNHG1 promotes MPP+-induced cytotoxicity by regulating PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells via sponging miR-153-3p

Biological Research ◽

10.1186/s40659-019-0267-y ◽

2020 ◽

Vol 53 (1) ◽

Cited By ~ 7

Author(s):

Jun Zhao ◽

Lijiao Geng ◽

Yong Chen ◽

Chunfang Wu

Keyword(s):

Signaling Pathway ◽

Regulatory Networks ◽

Mtor Signaling ◽

Luciferase Reporter ◽

Mtor Signaling Pathway ◽

Expression Levels ◽

Promising Therapeutic Target ◽

Rna Immunoprecipitation

Abstract Background Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson’s disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. Methods 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis. Results Increased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p. Conclusion SNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.

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MiR155 Affect the Cerebral Ischemic Injury by Rheb/mTOR Signaling Pathway

10.21203/rs.3.rs-1021026/v1 ◽

2021 ◽

Author(s):

Le Chang ◽

Yu-Ying Xue ◽

Xu-Rong Zhu ◽

Ye Tian ◽

Zhi-Qin Liu ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebral Infarction ◽

Signaling Pathway ◽

Neuronal Apoptosis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mtor Signaling ◽

Transcriptional Level ◽

Mtor Signaling Pathway ◽

Expression Levels

Abstract Ischemic stroke remains to be a leading cause of death and disability worldwide at present. Cerebral ischemia/reperfusion injury (CIRI) is a critical pathogenesis leading to a poor prognosis for ischemic stroke patients.Recent studies have found that miR155 may be involved in the occurrence of CIRI after stroke, but it’s role and specific mechanism are not completely clear.Therefore, this study investigated the effects of miR155 expression levels on mortality, cerebral infarction volume and neuronal apoptosis in MCAO/R rats by changing the expression level of miR155 in the ischemic penumbra (IP) region of rats. QRT-PCR and Western Blotting were used to detect the expression changes of Rheb, mTOR, 4EBP1 and S6K1 under different miR155 expression levels. The results showed that inhibition of miR155 could reduce the mortality, the volume of cerebral infarction and the number of neuronal apoptosis in MCAO/R rats.The mRNA and protein expressions of Rheb, mTOR, 4EBP1 and S6K1 were increased after inhibition of miR155, and vice versa. It suggested that inhibition the expression of miR155 could alleviate CIRI in the IP by activating Rheb/mTOR signaling at the transcriptional level. At the same time, we found that the phosphorylation level of mTOR signaling pathway were also increased after inhibition of miR155, indicating that autophagy level regulated by mTOR signaling pathway may be involved in the CIRI.

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