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JPMA. the Journal of the Pakistan... Sep 2021To measure and compare micro ribonucleic acid-16, survivin and tumour protein p53-regulated apoptosis-inducing protein 1 expression levels in preeclamptic and...
OBJECTIVE
To measure and compare micro ribonucleic acid-16, survivin and tumour protein p53-regulated apoptosis-inducing protein 1 expression levels in preeclamptic and normotensive pregnancies, and to check the correlation of micro ribonucleic acid-16 with messenger ribonucleic acid expression of survivin and tumour protein p53.
METHODS
The observational cross-sectional comparative study was conducted at the Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan, from 2016 to 2018, and comprised preeclamptic women in group A and normotensive women in group B. The preeclamptic patients were further categorised into early-onset preeclampsia subgroup A1and late-onset preeclampsia group A2. Expression of micro ribonucleic acid-16, messenger ribonucleic acid expression of survivin and tumour protein p53 in preeclamptic and normotensive pregnancies were analysed using real time polymerase chain reaction. Data was analysed using SPSS 22.
RESULTS
Of the 54 patients, 27(50%) were in each of the two groups. Within group A, 14(52%) patients were in group A1 and 13(48%) in group A2. The expression of micro ribonucleic acid 16 showed significant increase in group A compared to group B (p<0.05). The difference was not significant between the subgroups A1 and A2. The levels of messenger ribonucleic acid expression of survivin and tumour protein p53 were deregulated in group A, with a decrease in survivin and an increase in tumour protein p53. The messenger ribonucleic acid expression of survivin and tumour protein p53 showed statistically significant differences across subgroups A1 and A2 (p<0.05). The micro ribonucleic acid-16 expression correlated negatively with messenger ribonucleic acid expression of survivin, but exhibited a positive correlation with tumour protein p53.
CONCLUSIONS
Deregulated micro ribonucleic acid-16 along with differentially expressed apoptotic genes, survivin and tumour protein p53 might result in altered apoptosis implicated in the pathogenesis of preeclampsia.
Topics: Cross-Sectional Studies; Female; Humans; MicroRNAs; Pre-Eclampsia; Pregnancy; Survivin; Tumor Suppressor Protein p53
PubMed: 34580516
DOI: 10.47391/JPMA.1171 -
Asian Pacific Journal of Cancer... Nov 2021to assess expression of p27 and survivin in chronic gastritis with/without H. pylori ± intestinal metaplasia (IM) and in intestinal-type gastric cancer (IGC).
OBJECTIVE
to assess expression of p27 and survivin in chronic gastritis with/without H. pylori ± intestinal metaplasia (IM) and in intestinal-type gastric cancer (IGC).
MATERIALS AND METHODS
Immunohistochemical staining for p27 and survivin on paraffin-embedded sections of 20 chronic gastritis, 20 H. pylori gastritis, 15 H. pylori gastritis with IM, 50 IGC, and 10 controls. Positivity (number of positive cases) and expression (mean percentage of positive gastric cells) for both proteins were evaluated.
RESULTS
P27 positivity and expression decreased from control to chronic gastritis to H. pylori gastritis to H. pylori gastritis with IM. In IGC, p27 positivity and expression were lower than controls and chronic gastritis but higher than H. pylori gastritis ±IM. High grade and advanced stage IGCs have insignificantly lower p27 positivity and expression than low grade and early stage IGCs. By contrast, survivin positivity and expression increased from chronic gastritis to H. pylori gastritis to H. pylori gastritis with IM to IGCs. High grade and advanced stage IGCs have significantly higher survivin positivity and expression than low grade and early stage IGCs. Males have higher positivity and expression for p27 and survivin than females.
CONCLUSION
Inverse relation between p27 and survivin in H. pylori gastritis, H. pylori gastritis with IM and IGCs lesions, suggesting that both proteins could be used as potential prognostic and/or diagnostic biomarkers in H. pylori and IM associated- gastritis as well as in IGC.
Topics: Case-Control Studies; Chronic Disease; Cyclin-Dependent Kinase Inhibitor p27; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Prognosis; Retrospective Studies; Sex Factors; Stomach; Stomach Neoplasms; Survivin
PubMed: 34837912
DOI: 10.31557/APJCP.2021.22.11.3553 -
Journal of Experimental & Clinical... Aug 2019Survivin (also named BIRC5) is a well-known cancer therapeutic target. Since its discovery more than two decades ago, the use of survivin as a target for cancer... (Review)
Review
Survivin (also named BIRC5) is a well-known cancer therapeutic target. Since its discovery more than two decades ago, the use of survivin as a target for cancer therapeutics has remained a central goal of survivin studies in the cancer field. Many studies have provided intriguing insight into survivin's functional role in cancers, thus providing promise for survivin as a cancer therapeutic target. Despite this, moving survivin-targeting agents into and through the clinic remains a challenge. In order to address this challenge, we may need to rethink current strategies in order to develop a new mindset for targeting survivin. In this Review, we will first summarize the current survivin mechanistic studies, and then review the status of survivin cancer therapeutics, which is classified into five categories: (i) survivin-partner protein interaction inhibitors, (ii) survivin homodimerization inhibitors, (iii) survivin gene transcription inhibitors, (iv) survivin mRNA inhibitors and (v) survivin immunotherapy. We will then provide our opinions on cancer therapeutics using survivin as a target, with the goal of stimulating discussion that might facilitate translational research for discovering improved strategies and/or more effective anticancer agents that target survivin for cancer therapy.
Topics: Antineoplastic Agents; Humans; Molecular Targeted Therapy; Neoplasms; Prognosis; Survivin
PubMed: 31439015
DOI: 10.1186/s13046-019-1362-1 -
International Journal of Biological... 2018CD44, also known as homing cell adhesion molecule is a multi-structural cell molecule involved in cell-cell and cell-extracellular matrix communications. CD44 regulates... (Review)
Review
CD44, also known as homing cell adhesion molecule is a multi-structural cell molecule involved in cell-cell and cell-extracellular matrix communications. CD44 regulates a number of central signaling pathways, including PI3K/AKT, Rho GTPases and the Ras-MAPK pathways, but also acts as a growth/arrest sensor, and inhibitor of angiogenesis and invasion, in response to signals from the microenvironment. The function of CD44 has been very controversial since it acts as both, a suppressor and a promoter of tumor growth and progression. To address this discrepancy, we have previously established CD44-inducible system both and . Next, using microarray analysis, we have identified and validated Survivin, Cortactin and TGF-β2 as novel CD44-downstream target genes, and characterized their signaling pathways underpinning CD44-promoted breast cancer (BC) cell invasion. This report aims to update the literature by adding and discussing the impact of these novel three signaling pathways to better understand the CD44-signaling pathways involved in BC tumor cell invasion.
Topics: Breast Neoplasms; Cortactin; Female; Humans; Hyaluronan Receptors; Signal Transduction; Survivin; rho GTP-Binding Proteins
PubMed: 30443182
DOI: 10.7150/ijbs.23586 -
International Journal of Biological... 2024Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. Despite continuous improvement in treatment strategies, recurrence or...
Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. Despite continuous improvement in treatment strategies, recurrence or persistence of cancer after radiotherapy is still inevitable, highlighting the need to identify therapeutic resistance factors and develop effective methods for NPC treatment. Herein, we found that TRAF4 is overexpressed in NPC cells and tissues. Knockdown TRAF4 significantly increased the radiosensitivity of NPC cells, possibly by inhibiting the Akt/Wee1/CDK1 axis, thereby suppressing survivin phosphorylation and promoting its degradation by FBXL7. TRAF4 is positively correlated with p-Akt and survivin in NPC tissues. High protein levels of TRAF4 were observed in acquired radioresistant NPC cells, and knockdown of TRAF4 overcomes radioresistant and the xenograft mouse model. Altogether, our study highlights the TRAF4-survivin axis as a potential therapeutic target for radiosensitization in NPC.
Topics: Humans; Animals; Mice; Carcinoma; Nasopharyngeal Neoplasms; Proto-Oncogene Proteins c-akt; Survivin; TNF Receptor-Associated Factor 4; Signal Transduction; Nasopharyngeal Carcinoma; Ubiquitination
PubMed: 38164179
DOI: 10.7150/ijbs.87180 -
CNS Neuroscience & Therapeutics Apr 2024Cognitive impairment is associated with reduced hippocampal neurogenesis; however, the causes of decreased hippocampal neurogenesis remain highly controversial. Here, we...
AIMS
Cognitive impairment is associated with reduced hippocampal neurogenesis; however, the causes of decreased hippocampal neurogenesis remain highly controversial. Here, we investigated the role of survivin in the modulation of hippocampal neurogenesis in AD.
METHODS
To investigate the effect of survivin on neurogenesis in neural stem cells (NSCs), we treated mouse embryonic NSCs with a survivin inhibitor (YM155) and adeno-associated viral survivin (AAV-Survivin). To explore the potential role of survivin expression in AD, AAV9-Survivin or AAV9-GFP were injected into the dentate gyrus (DG) of hippocampus of 7-month-old wild-type and 5XFAD mice. Cognitive function was measured by the Y maze and Morris water maze. Neurogenesis was investigated by BrdU staining, immature, and mature neuron markers.
RESULTS
Our results indicate that suppression of survivin expression resulted in decreased neurogenesis. Conversely, overexpression of survivin using AAV-Survivin restored neurogenesis in NSCs that had been suppressed by YM155 treatment. Furthermore, the expression level of survivin decreased in the 9-month-old 5XFAD compared with that in wild-type mice. AAV-Survivin-mediated overexpression of survivin in the DG in 5XFAD mice enhanced neurogenesis and cognitive function.
CONCLUSION
Hippocampal neurogenesis can be enhanced by survivin overexpression, suggesting that survivin could serve as a promising therapeutic target for the treatment of AD.
Topics: Animals; Mice; Alzheimer Disease; Cognition; Disease Models, Animal; Hippocampus; Mice, Transgenic; Neurogenesis; Survivin
PubMed: 37904343
DOI: 10.1111/cns.14509 -
Histology and Histopathology Jan 2015The tumor microenvironment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Factors released by... (Review)
Review
The tumor microenvironment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Factors released by tumor cells themselves contribute in creating an environment mostly favorable but sometimes detrimental to the tumor. Survivin, one of the key members of the inhibitor of apoptosis (IAP) family of proteins, has been shown in the cytoplasm, mitochondria, nucleus, and most recently in the extracellular space, transported via small membrane bound vesicles called exosomes. Exosomes are secreted from hematopoietic, non-hematopoietic, tumor, and non-tumor cells, shuttling essential molecules such as proteins, RNAs, and microRNAs, all believed to be important for cell-cell and cell-extracellular communication. In this review, we discuss exosomal Survivin and its role in modifying the tumor microenvironment.
Topics: Exosomes; Humans; Inhibitor of Apoptosis Proteins; Neoplasms; Survivin; Tumor Microenvironment
PubMed: 25020159
DOI: 10.14670/HH-30.43 -
International Journal of Molecular... Aug 2023Ubiquitin-specific protease 2 (USP2) is a deubiquitinase belonging to the USPs subfamily. USP2 has been known to display various biological effects including...
Ubiquitin-specific protease 2 (USP2) is a deubiquitinase belonging to the USPs subfamily. USP2 has been known to display various biological effects including tumorigenesis and inflammation. Therefore, we aimed to examine the sensitization effect of USP2 in TRAIL-mediated apoptosis. The pharmacological inhibitor (ML364) and siRNA targeting enhanced TNF-related apoptosis-inducing ligand (TRAIL)-induced cancer cell death, but not normal cells. Mechanistically, USP2 interacted with survivin, and ML364 degraded survivin protein expression by increasing the ubiquitination of survivin. Overexpression of survivin or USP2 significantly prevented apoptosis through cotreatment with ML364 and TRAIL, whereas a knockdown of increased sensitivity to TRAIL. Taken together, our data suggested that ML364 ubiquitylates and degrades survivin, thereby increasing the reactivity to TRAIL-mediated apoptosis in cancer cells.
Topics: Humans; Down-Regulation; TNF-Related Apoptosis-Inducing Ligand; Survivin; Cell Death; Neoplasms; Ubiquitin Thiolesterase
PubMed: 37628997
DOI: 10.3390/ijms241612816 -
Journal of Experimental & Clinical... Mar 2021Dedifferentiated liposarcoma (DDLPS), a tumor that lacks effective treatment strategies and is associated with poor outcomes, expresses amplified MDM2 in the presence of...
Selinexor versus doxorubicin in dedifferentiated liposarcoma PDXs: evidence of greater activity and apoptotic response dependent on p53 nuclear accumulation and survivin down-regulation.
BACKGROUND
Dedifferentiated liposarcoma (DDLPS), a tumor that lacks effective treatment strategies and is associated with poor outcomes, expresses amplified MDM2 in the presence of wild-type p53. MDM2 ubiquitination of p53 facilitates its XPO1-mediated nuclear export, thus limiting p53 tumor suppressor functions. Consequently, nuclear export is a rational target in DDLPS. We directly compared the antitumor activity of the first-in class XPO1 inhibitor selinexor and doxorubicin, the standard front-line therapy in sarcomas, in DDLPS patient-derived xenografts (PDXs) and primary cell lines.
METHODS
Drug activity was assessed in three PDXs (and two corresponding cell lines) established from the dedifferentiated component of primary untreated retroperitoneal DDLPS with myogenic (N = 2) and rhabdomyoblastic (N = 1) differentiation from patients who underwent surgery. These models were marked by amplification of MDM2, CDK4 and HMGA2 genes.
RESULTS
Selinexor was moderately active in the three PDXs but achieved greater tumor response compared to doxorubicin (maximum tumor volume inhibition: 46-80 % vs. 37-60 %). The PDX harboring rhabdomyoblastic dedifferentiation showed the highest sensitivity to both agents. PDX response to selinexor and doxorubicin was not associated with the extent of MDM2 and CDK4 gene amplification. Interestingly, the most chemosensitive PDX model showed the lowest extent of HMGA2 amplification. Selinexor was also more efficient than doxorubicinin in inducing an apoptotic response in PDXs and cell lines. Consistently, an increased nuclear accumulation of p53 was seen in all selinexor-treated models. In addition, a time-dependent decrease of survivin expression, with an almost complete abrogation of the cytoplasmic anti-apoptotic pool of this protein, was observed as a consequence of the decreased acetylation/activation of STAT3 and the increased ubiquitination of nuclear survivin.
CONCLUSIONS
Selinexor showed a moderate antitumor activity in three DDLPS PDXs, which was, however, consistently higher than doxorubicin across all different models regardless the extent of MDM2 amplification and the histological differentiation. The depletion of survivin protein seems to significantly contribute to the induction of apoptosis through which selinexor exerts its antitumor activity.
Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Cell Dedifferentiation; Cell Nucleus; Down-Regulation; Doxorubicin; Humans; Hydrazines; Liposarcoma; Male; Mice; Mice, Nude; Random Allocation; Survivin; Triazoles; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays
PubMed: 33648535
DOI: 10.1186/s13046-021-01886-x -
Cell Death & Disease Sep 2022Ubiquitin-specific protease 1 (USP1) is a deubiquitinase involved in DNA damage repair by modulating the ubiquitination of major regulators, such as PCNA and FANCD2....
Ubiquitin-specific protease 1 (USP1) is a deubiquitinase involved in DNA damage repair by modulating the ubiquitination of major regulators, such as PCNA and FANCD2. Because USP1 is highly expressed in many cancers, dysregulation of USP1 contributes to cancer therapy. However, the role of USP1 and the mechanisms underlying chemotherapy remain unclear. In this study, we found high USP1 expression in tumor tissues and that it correlated with poor prognosis in RCC. Mechanistically, USP1 enhanced survivin stabilization by removing ubiquitin. Pharmacological inhibitors (ML23 and pimozide) and siRNA targeting USP1 induced downregulation of survivin expression. In addition, ML323 upregulated DR5 expression by decreasing miR-216a-5p expression at the post-transcriptional level, and miR-216a-5p mimics suppressed the upregulation of DR5 by ML323. Inhibition of USP1 sensitized cancer cells. Overexpression of survivin or knockdown of DR5 markedly prevented the co-treatment with ML323 and TRAIL-induced apoptosis. These results of in vitro were proved in a mouse xenograft model, in which combined treatment significantly reduced tumor size and induced survivin downregulation and DR5 upregulation. Furthermore, USP1 and survivin protein expression showed a positive correlation, whereas miR-216a-5p and DR5 were inversely correlated in RCC tumor tissues. Taken together, our results suggest two target substrates of USP1 and demonstrate the involvement of survivin and DR5 in USP1-targeted chemotherapy.
Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Renal Cell; Cell Line, Tumor; Deubiquitinating Enzymes; Down-Regulation; Humans; Kidney Neoplasms; Mice; MicroRNAs; Pimozide; Proliferating Cell Nuclear Antigen; RNA, Small Interfering; Receptors, TNF-Related Apoptosis-Inducing Ligand; Survivin; Ubiquitin-Specific Proteases; Ubiquitins; Up-Regulation
PubMed: 36153316
DOI: 10.1038/s41419-022-05271-0