scholarly journals SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway

2014 ◽  
Vol 5 (5) ◽  
pp. e1247-e1247 ◽  
Author(s):  
L-J Yuan ◽  
J-D Li ◽  
L Zhang ◽  
J-H Wang ◽  
T Wan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Cell Function ◽  
Disease Free Survival ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway

Abstract Previously, we found that sperm-associated antigen 5 (SPAG5) was upregulated in pelvic lymph node metastasis–positive cervical cancer. The aim of this study is to examine the role of SPAG5 in the proliferation and tumorigenicity of cervical cancer and its clinical significance in tumor progression. In our study, SPAG5 expression in cervical cancer patients was detected using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry; cervical cancer cell function with downregulated SPAG5 in vitro was explored using tetrazolium assay, flow cytometry, and colony formation and Transwell assays. SPAG5 was upregulated in tumor tissue compared with paired adjacent noncancerous tissues; SPAG5 upregulation in tumor tissues indicated poor disease-free survival, which was also an independent prognostic indicator for cervical cancer patients. In vitro study demonstrated that SPAG5 downregulation inhibited cell proliferation and growth significantly by G2/M arrest and induction of apoptosis, and hindered cell migration and invasion. Under SPAG5 downregulation, the sensitivity of cervical cancer cells differed according to taxol dose, which correlated with mammalian target of rapamycin (mTOR) signaling pathway activity. In general, SPAG5 upregulation relates to poor prognosis in cervical cancer patients, and SPAG5 is a regulator of mTOR activity during taxol treatment in cervical cancer.

scholarly journals MicroRNA-1271-5p inhibits the tumorigenesis of ovarian cancer through targeting E2F5 and negatively regulates the mTOR signaling pathway

2020 ◽  
Author(s):  
Qin Li ◽  
Junyu Shi ◽  
Xiaoli Xu
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Mtor Signaling ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Direct Target ◽  
The Relationship

Abstract Background: MicroRNA-1271-5p (miR-1271-5p) has been reported to participate in the progression of many human cancers. However, the role of miR-1271-5p still remains unclear in ovarian cancer (OC). Therefore, we explored the effect of miR-1271-5p on the development of OC in present study. Methods: We measured the miR-1271-5p expression via the qRT-PCR assay. Then the function of miR-1271-5p was analyzed through MTT and Transwell assays. The relationship among miR-1271-5p and E2F5 was verified by dual luciferase assay. The protein expression levels were examined through western blot.Results: MiR-1271-5p was downregulated in OC tissues which predicted poor prognosis of OC patients. Moreover, E2F5 was a direct target of miR-1271-5p in OC. And miR-1271-5p suppressed cell proliferation, migration and invasion in OC through targeting E2F5. Furthermore, E2F5 was upregulated in OC tissues which predicted poor prognosis of OC patients. Besides that, miR-1271-5p suppressed EMT and mTOR pathway in OC. Conclusion: MiR-1271-5p inhibited the tumorigenesis of OC through targeting E2F5 and negatively regulated the mTOR signaling pathway.

scholarly journals MicroRNA-199a Inhibits Cell Proliferation, Migration, and Invasion and Activates AKT/mTOR Signaling Pathway by Targeting B7-H3 in Cervical Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382094224
Author(s):  
Xiang Yang ◽  
Kai-Xun Feng ◽  
Hu Li ◽  
Li Wang ◽  
Hong Xia
Keyword(s):  
Cervical Cancer ◽  
Signaling Pathway ◽  
Untranslated Region ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Chain Reaction ◽  
Normal Tissues ◽  
Polymerase Chain ◽  
Cancer Tissues

Cervical cancer is a deadly disease. Some microRNAs are involved in tumor invasion and metastasis. Decreased expression of microRNA-199a has been correlated with tumorigenesis. In our study, the quantitative real-time polymerase chain reaction results indicated that microRNA-199a was expressed at lower levels in cervical cancer tissues, and the expression level of B7-H3 was significantly increased compared with that in the adjacent normal tissues, and the expression levels of B7-H3 and microRNA-199a in cervical cancer tissues and in adjacent normal tissues were inversely correlated. We also found that the expression of microRNA-199a was downregulated in cervical cancer cell lines when compared to immortalized cells. In this study, B7-H3 was identified as a novel target of microRNA-199a in cervical cancer. TargetScan ( http://www.targetscan.org/ ) bioinformatics analysis was used to predict that the 3′-untranslated region of B7-H3 is a direct target of microRNA-199a. The result was also verified by the luciferase reporter assay. MicroRNA-199a could directly target the 3′-untranslated region of B7-H3, but the specific signaling pathways that were involved in regulating B7-H3 expression remained unclear. To clarify whether the suppressive effect of microRNA-199a was mediated through B7-H3, a series of experiments were performed. We found that the overexpression of microRNA-199a inhibited cell proliferation, migration, and invasion via direct binding to B7-H3. Epithelial–mesenchymal transition is a major factor involved in cervical cancer metastasis. Quantitative real-time polymerase chain reaction and western blot results indicated that microRNA-199a inhibits tumor progression in cervical cancer by targeting B7-H3. The microRNAs regulatory network is quite complex. We further examined the effect of microRNA-199a on the AKT/mTOR signaling pathway. We explored the regulatory role of microRNA-199a and first demonstrated that highly expressed microRNA-199a inhibits tumor growth and activates the AKT/mTOR signaling pathway by targeting B7-H3 in vivo and in vitro. Our findings not only provide a better understanding of the pathogenesis of cervical cancer but also provide novel findings and theoretical support for potential targeted therapeutic tools for cervical cancer.

scholarly journals Knockdown of DIAPH3 Inhibits the Proliferation of Cervical Cancer Cells through Inactivating mTOR Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Linling Wan ◽  
Jiamin Zhu ◽  
Qunying Wu
Keyword(s):  
Cervical Cancer ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Poor Overall Survival ◽  
Western Blot Assay ◽  
Incidence And Mortality

Cervical cancer (CC) ranks fourth for both incidence and mortality among females in worldwide. Therefore, it is urgent to explore new therapeutic and diagnostic targets for cervical cancer. Diaphanous-related formin 3 (DIAPH3) has been identified to play crucial roles in many malignant tumors. But its function and potential mechanism in CC remain largely unknown. In our study, DIAPH3 was frequently upregulated in CC tissue samples and increased expression of DIAPH3 was associated with poor overall survival according to several databases. Through in vitro and in vivo experiments, we found that decreased expression levels of DIAPH3 significantly inhibited the progression of CC. The GSEA analysis and western blot assay indicated that DIAPH3 was associated with the mTOR signaling pathway. The univariate and multivariate Cox analysis indicated that DIAPH3 was an independent prognosis risk factor in TCGA-CESC. And we confirmed that DIAPH3 expression was clearly related to tumor immune infiltrating cells (TIICs) by the analysis of CIBERSORT and TIMER databases. Taken together, we revealed that DIAPH3 plays as an oncogene through mTOR signaling pathway and DIAPH3 might be a potential prognostic biomarker in CC.

scholarly journals Kinesin family member 18B regulates the proliferation and invasion of human prostate cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yu-Peng Wu ◽  
Zhi-Bin Ke ◽  
Wen-Cai Zheng ◽  
Ye-Hui Chen ◽  
Jun-Ming Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family Member ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Mouse Xenograft Model ◽  
Kinesin Family

AbstractExpression of kinesin family member 18B (KIF18B), an ATPase with key roles in cell division, is deregulated in many cancers, but its involvement in prostate cancer (PCa) is unclear. Here, we investigated the expression and function of KIF18B in human PCa specimens and cell lines using bioinformatics analyses, immunohistochemical and immunofluorescence microscopy, and RT-qPCR and western blot analyses. KIF18B was overexpressed in PCa specimens compared with paracancerous tissues and was associated with poorer disease-free survival. In vitro, KIF18B knockdown in PCa cell lines promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, while KIF18B overexpression had the opposite effects. In a mouse xenograft model, KIF18B overexpression accelerated and promoted the growth of PCa tumors. Bioinformatics analysis of control and KIF18B-overexpressing PCa cells showed that genes involved in the PI3K–AKT–mTOR signaling pathway were significantly enriched among the differentially expressed genes. Consistent with this observation, we found that KIF18B overexpression activates the PI3K–AKT–mTOR signaling pathway in PCa cells both in vitro and in vivo. Collectively, our results suggest that KIF18B plays a crucial role in PCa via activation of the PI3K–AKT–mTOR signaling pathway, and raise the possibility that KIF18B could have utility as a novel biomarker for PCa.

scholarly journals Histone demethylase KDM4A plays an oncogenic role in nasopharyngeal carcinoma by promoting cell migration and invasion

2021 ◽  
Author(s):  
Jingyi Zhao ◽  
Bingyan Li ◽  
Yongxia Ren ◽  
Tiansong Liang ◽  
Juan Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Tumor Formation ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Mtor Signaling Pathway ◽  
Tissue Samples

AbstractCompelling evidence has indicated the vital role of lysine-specific demethylase 4 A (KDM4A), hypoxia-inducible factor-1α (HIF1α) and the mechanistic target of rapamycin (mTOR) signaling pathway in nasopharyngeal carcinoma (NPC). Therefore, we aimed to investigate whether KDM4A affects NPC progression by regulating the HIF1α/DDIT4/mTOR signaling pathway. First, NPC and adjacent tissue samples were collected, and KDM4A protein expression was examined by immunohistochemistry. Then, the interactions among KDM4A, HIF1α and DDIT4 were assessed. Gain- and loss-of-function approaches were used to alter KDM4A, HIF1α and DDIT4 expression in NPC cells. The mechanism of KDM4A in NPC was evaluated both in vivo and in vitro via RT-qPCR, Western blot analysis, MTT assay, Transwell assay, flow cytometry and tumor formation experiments. KDM4A, HIF1α, and DDIT4 were highly expressed in NPC tissues and cells. Mechanistically, KDM4A inhibited the enrichment of histone H3 lysine 9 trimethylation (H3K9me3) in the HIF1α promoter region and thus inhibited the methylation of HIF1α to promote HIF1α expression, thus upregulating DDIT4 and activating the mTOR signaling pathway. Overexpression of KDM4A, HIF1α, or DDIT4 or activation of the mTOR signaling pathway promoted SUNE1 cell proliferation, migration, and invasion but inhibited apoptosis. KDM4A silencing blocked the mTOR signaling pathway by inhibiting the HIF1α/DDIT4 axis to inhibit the growth of SUNE1 cells in vivo. Collectively, KDM4A silencing could inhibit NPC progression by blocking the activation of the HIF1α/DDIT4/mTOR signaling pathway by increasing H3K9me3, highlighting a promising therapeutic target for NPC.

Targeting mammalian target of rapamycin: prospects for the treatment of inflammatory bowel diseases

2020 ◽  
Vol 27 ◽  
Author(s):  
Naser-Aldin Lashgari ◽  
Nazanin Momeni Roudsari ◽  
Saeideh Momtaz ◽  
Negar Ghanaatian ◽  
Parichehr Kohansal ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
In Vivo Studies ◽  
Cochrane Library ◽  
Mtor Signaling Pathway ◽  
Inflammatory Bowel

: Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders. Several cellular and biomolecular pathways are implicated in the pathogenesis of IBD, yet the etiology is unclear. Activation of the mammalian target of rapamycin (mTOR) pathway in the intestinal epithelial cells was also shown to induce inflammation. This review focuses on the inhibition of the mTOR signaling pathway and its potential application in treating IBD. We also provide an overview on plant-derived compounds that are beneficial for the IBD management through modulation of the mTOR pathway. Data were extracted from clinical, in vitro and in vivo studies published in English between 1995 and May 2019, which were collected from PubMed, Google Scholar, Scopus and Cochrane library databases. Results of various studies implied that inhibition of the mTOR signaling pathway downregulates the inflammatory processes and cytokines involved in IBD. In this context, a number of natural products might reverse the pathological features of the disease. Furthermore, mTOR provides a novel drug target for IBD. Comprehensive clinical studies are required to confirm the efficacy of mTOR inhibitors in treating IBD.

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