Papers by Subbroto K Saha
Journal of Biochemistry and Molecular Biology, Oct 31, 2021
EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor... more EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor and promoter activities, making it an appealing target for cancer therapy. Here, we used a systematic multi-omics analysis to review the expression of EGR1 and its role in regulating clinical outcomes in breast cancer (BC). EGR1 expression, its promoter methylation, and protein expression pattern were assessed using various publicly available tools. COSMIC-based somatic mutations and cBioPortal-based copy number alterations were analyzed, and the prognostic roles of EGR1 in BC were determined using Prognoscan and Kaplan-Meier Plotter. We also used bc-GenEx-Miner to investigate the EGR1 co-expression profile. EGR1 was more often downregulated in BC tissues than in normal breast tissue, and its knockdown was positively correlated with poor survival. Low EGR1 expression levels were also associated with increased risk of ER+, PR+, and HER2-BCs. High positive correlations were observed among EGR1, DUSP1, FOS, FOSB, CYR61, and JUN mRNA expression in BC tissue. This systematic review suggested that EGR1 expression may serve as a prognostic marker for BC patients and that clinicopathological parameters influence its prognostic utility. In addition to EGR1, DUSP1, FOS, FOSB, CYR61, and JUN can jointly be considered prognostic indicators for BC. [BMB Reports 2021; 54(10): 497-504]
Journal of diabetes mellitus, 2012
This study was undertaken to evaluate the hypoglycemic and hypolipidemic effect of Momordica char... more This study was undertaken to evaluate the hypoglycemic and hypolipidemic effect of Momordica charantia (wild and hybrid variety) powder on alloxan induced type 2 diabetic male Long-Evans rats. Oral feeding of the M. charantia powder slightly decreased serum total cholesterol, triglyceride levels and LDL-cholesterol compared with wild, hybrid and standard drug. M. charantia wild variety showed more significant (p < 0.05, 0.01, 0.001) effect on blood glucose level when compared with hybrid variety and standard drug (glibenclamide, 5 mg/kg). At the same time rats' serum insulin level markedly increased, wild variety showed more significant (p < 0.05, 0.01, 0.001) than glibenclamide control group and hybrid group. But M. charantia did not show any significant effect on HDL-cholesterol and liver glycogen. Thus, results of the study prove that the wild variety of M. charantia fruit have potent antidiabetic and antilipidemic property.
Journal of Personalized Medicine, Sep 1, 2020
Scientific Reports, Oct 4, 2018
OCT4 is a master transcription factor that regulates the pluripotency of pluripotent stem cells a... more OCT4 is a master transcription factor that regulates the pluripotency of pluripotent stem cells and cancer stem cells along with other factors, including SOX2, KLF4, and C-MYC. Three different transcripts, OCT4A, OCT4B, and OCT4B1, are known to be generated by alternative splicing and eight OCT4 pseudogenes have been found in the human genome. Among them, we examined OCT4 and three pseudogenes (POU5F1P1, POU5F1P3, and POU5F1P4) because of their high expression possibility in cancer. In addition, previous studies indicated that OCT4 expression is augmented in cervical cancer and associated with poor prognosis, whereas OCT4 is down-regulated and correlated with good clinical outcomes in breast cancer. Because of these conflicting reports, we systematically evaluated whether expression of OCT4 and its pseudogenes can serve as oncogenic markers in various human cancers using the Oncomine database. Moreover, copy number alterations and mutations in OCT4 gene and its pseudogenes were analyzed using cBioPortal and the relationship between expression of OCT4 and pseudogenes and survival probability of cancer patients were explored using Kaplan-Meier plotter, OncoLnc, PROGgeneV2, and PrognoScan databases. Multivariate survival analysis was further conducted to determine the risk of the expression of the occurrence of OCT4 and its pseudogenes on certain cancer types using data from the Kaplan-Meier plotter. Overall, an association between expression of OCT4 and pseudogenes and cancer prognosis were established, which may serve as a therapeutic target for various human cancers. Approximately 14.1 million new cancer cases and 8.2 million deaths occurred worldwide in 2012 1 and, by 2030, the universal burden is anticipated to increase to 21.7 million new cancer cases and 13 million cancer deaths because of aging and growth of the population 2,3. Thus, cancer has become a major cause of death for humans. Cancer occurrence has various causes, all of which are related to a specific class of genes called proto-oncogenes or oncogenes. A proto-oncogene can be transformed into an oncogene. Activation of a proto-oncogene into an oncogene can occur through a point mutation, gene amplification, or gene translocation 4. These mutations can alter the DNA copy number and gene function at various locations of a specific genome 5-7. Pollack et al. reported that copy number alterations (CNAs) affect gene expression, which may be a critical component of tumor progression 7,8. Detecting CNAs may enable researchers to relate a CNA with a disease phenotype 7,9 , providing a basis for clinicians and scientists to identify new biomarkers or signaling pathways in cancer for therapeutics development or early interference to prevent cancer 7. A transcription factor (TF), octamer-binding transcription factor 4 (OCT4), also known as POU (Pituitary-specific Pit-1, Octamer (ATGCAAAT) transcription factor, and neural Unc-86 transcription factor) domain class 5 Homeobox transcription factor 1 (POU5F1), regulates the pluripotency of pluripotent stem cells 10. OCT4 was also reported to be highly expressed in several other types of cancer cells. However, numerous previous reports showed opposite functions of the OCT4 gene; some studies revealed that under-expression of OCT4
Cancer Gene Therapy, Jun 5, 2019
Prominin 1 (PROM1) is considered a biomarker for cancer stem cells, although its biological role ... more Prominin 1 (PROM1) is considered a biomarker for cancer stem cells, although its biological role is unclear. Prominin 2 (PROM2) has also been associated with certain cancers. However, the prognostic value of PROM1 and PROM2 in cancer is controversial. Here, we performed a systematic data analysis to examine whether prominins can function as prognostic markers in human cancers. The expression of prominins was assessed and their prognostic value in human cancers was determined using univariate and multivariate survival analyses, via various online platforms. We selected a group of prominent functional protein partners of prominins by protein-protein interaction analysis. Subsequently, we investigated the relationship between mutations and copy number alterations in prominin genes and various types of cancers. Furthermore, we identified genes that correlated with PROM1 and PROM2 in certain cancers, based on their levels of expression. Gene ontology and pathway analyses were performed to assess the effect of these correlated genes on various cancers. We observed that PROM1 was frequently overexpressed in esophageal, liver, and ovarian cancers and its expression was negatively associated with prognosis, whereas PROM2 overexpression was associated with poor overall survival in lung and ovarian cancers. Based on the varying characteristics of prominins, we conclude that PROM1 and PROM2 expression differentially modulates the clinical outcomes of cancers.
Biotechnology Journal, May 15, 2014
Nano-scale materials are noted for unique properties, distinct from those of their bulk material ... more Nano-scale materials are noted for unique properties, distinct from those of their bulk material equivalents. In this study, we prepared spherical silver nanoparticles (AgNPs) with an average size of about 30 nm and tested their potency to induce neuronal differentiation of SH-SY5Y cells. Human neuroblastoma SH-SY5Y cells are considered an ideal in vitro model for studying neurogenesis, as they can be maintained in an undifferentiated state or be induced to differentiate into neuron-like phenotypes in vitro by several differentiation-inducing agents. Treatment of SH-SY5Y cells by biologically synthesized AgNPs led to cell morphological changes and significant increase in neurite length and enhanced the expression of neuronal differentiation markers such as Map-2, β-tubulin III, synaptophysin, neurogenin-1, Gap-43, and Drd-2. Furthermore, we observed an increase in generation of intracellular reactive oxygen species (ROS), activation of several kinases such as ERK and AKT, and downregulation of expression of dual-specificity phosphatases (DUSPs) in AgNP-exposed SH-SY5Y cells. Our results suggest that AgNPs modulate the intracellular signaling pathways, leading to neuronal differentiation, and could be applied as promising nanomaterials for stem cell research and therapy.
Journal of Personalized Medicine, Dec 2, 2020
ATP/GTP binding protein 1 (AGTPBP1) encodes a crucial protein, cytosolic carboxypeptidase 1 (CCP1... more ATP/GTP binding protein 1 (AGTPBP1) encodes a crucial protein, cytosolic carboxypeptidase 1 (CCP1), which plays a role in modulating the polyglutamylation of tubulin and has been studied in degenerative diseases. However, the role of AGTPBP1 in malignancy has not been completely studied yet. In this study, we examined the role of AGTPBP1 in cancer progression, its association with patient survival, and related mechanisms in lung cancer, using the A549 cell line and lung cancer gene expression datasets. AGTPBP1 knockdown increased the proliferation, migration, sphere formation, and drug resistance of A549 cells. Lung cancer datasets revealed significantly lower mRNA and protein expression levels of AGTPBP1 in lung cancer tissues, as compared to those in normal tissues. Importantly, AGTPBP1 expression positively correlated with patient survival. Analysis of co-expressed genes revealed that AGTPBP1 expression positively correlated with immune infiltration in lung cancer. Our results conclusively suggested that AGTPBP1 expression was correlated with cancer progression and immune infiltration in lung cancer.
International Journal of Molecular Sciences
The expression of GPR50 in CSLC and several breast cancer cell lines was assessed by RT-PCR and o... more The expression of GPR50 in CSLC and several breast cancer cell lines was assessed by RT-PCR and online platform (UALCAN, GEPIA, and R2 gene analysis). The role of GPR50 in driving CSLC, sphere formation, cell proliferation, and migration was performed using shGPR50 gene knockdown, and the role of GPR50-regulated signaling pathways was examined by Western blotting and Luciferase Assay. Herein, we confirmed that the expression of G protein-coupled receptor 50 (GPR50) in cancer stem-like cells (CSLC) is higher than that in other cancer cells. We examined that the knockdown of GPR50 in CSLC led to decreased cancer properties, such as sphere formation, cell proliferation, migration, and stemness. GPR50 silencing downregulates NF-kB signaling, which is involved in sphere formation and aggressiveness of CSLC. In addition, we demonstrated that GPR50 also regulates ADAM-17 activity by activating NOTCH signaling pathways through the AKT/SP1 axis in CSLC. Overall, we demonstrated a novel GPR50...
Journal of Personalized Medicine, 2021
The Sry-related HMG BOX (SOX) gene family encodes transcription factors containing highly conserv... more The Sry-related HMG BOX (SOX) gene family encodes transcription factors containing highly conserved high-mobility group domains that bind to the minor groove in DNA. Although some SOX genes are known to be associated with tumorigenesis and cancer progression, their expression and prognostic value have not been systematically studied. We performed multi-omic analysis to investigate the expression of SOX genes in human cancers. Expression and phylogenetic tree analyses of the SOX gene family revealed that the expression of three closely related SOX members, SOX4, SOX11, and SOX12, was increased in multiple cancers. Expression, mutation, and alteration of the three SOX members were evaluated using the Oncomine and cBioPortal databases, and the correlation between these genes and clinical outcomes in various cancers was examined using the Kaplan–Meier, PrognoScan, and R2 database analyses. The genes commonly correlated with the three SOX members were categorized in key pathways related ...
Journal of Clinical Medicine, 2020
The complexity of interstitial cystitis/bladder pain syndrome (IC/BPS) has led to considerable un... more The complexity of interstitial cystitis/bladder pain syndrome (IC/BPS) has led to considerable uncertainty in terms of diagnosis and prevalence of the condition. Here, we try to identify the IC/BPS-associated genes through an integrated analysis of Gene Expression Omnibus (GEO) datasets and confirm experimentally to predict the pathologic diagnosis of IC/BPS. Data mining analysis of GEO datasets (GSE621, GSE11783, GSE28242, and GSE57560) revealed a total of 53 (51 upregulated and two downregulated) common differentially expressed genes (DEGs) in IC/BPS. A protein–protein interaction (PPI) network was then constructed with the 53 common DEGs using Cytoscape v3.7.2, and subsequently, six hub genes (CD5, CD38, ITGAL, IL7R, KLRB1, and IL7R) were identified using cytoHubba v0.1 that were upregulated in IC/BPS. Enrichment analysis of common DEGs revealed that hematopoietic cell lineage, immune system, and T-cell receptor (TCR) signaling in naïve CD4+ T cell signaling pathways were promine...
Molecular Therapy - Oncolytics, 2020
Hepatocellular carcinoma (HCC) is a leading cause of cancerrelated death worldwide, and it is thu... more Hepatocellular carcinoma (HCC) is a leading cause of cancerrelated death worldwide, and it is thus critical to identify novel molecular biomarkers of HCC prognosis and elucidate the molecular mechanisms underlying HCC progression. Here, we show that G-protein-coupled receptor 50 (GPR50) in HCC is overexpressed and that GPR50 knockdown may downregulate cancer cell progression through attenuation of the Notch signaling pathway. GPR50 knockdown was found to reduce HCC progression by inactivating Notch signaling in a ligand-independent manner through a disintegrin and metalloproteinase metallopeptidase domain 17 (ADAM17), a proteolytic enzyme that cleaves the Notch receptor, which was corroborated by GPR50 overexpression in hepatocytes. GPR50 silencing also downregulated transcription and translation of ADAM17 through the AKT/specificity protein-1 (SP1) signaling axis. Notably, GPR50 was found to directly interact with ADAM17. Overall, we demonstrate a novel GPR50mediated regulation of the ADAM17-Notch signaling pathway, which can provide insights into HCC progression and prognosis and development of Notch-based HCC treatment strategies.
Frontiers in Cell and Developmental Biology, 2020
Autophagy, a cellular self-digestion process that is activated in response to stress, has a funct... more Autophagy, a cellular self-digestion process that is activated in response to stress, has a functional role in tumor formation and progression. Cancer stem cells (CSCs) accounting for a minor proportion of total cancer cells-have distinct self-renewal and differentiation abilities and promote metastasis. Researchers have shown that a numeral number of natural products using traditional experimental methods have been revealed to target CSCs. However, the specific role of autophagy with respect to CSCs and tumorigenesis using natural products are still unknown. Currently, CSCs are considered to be one of the causative reasons underlying the failure of anticancer treatment as a result of tumor recurrence, metastasis, and chemo-or radio-resistance. Autophagy may play a dual role in CSC-related resistance to anticancer treatment; it is responsible for cell fate determination and the targeted degradation of transcription factors via growth arrest. It has been established that autophagy promotes drug resistance, dormancy, and stemness and maintenance of CSCs. Surprisingly, numerous studies have also suggested that autophagy can facilitate the loss of stemness in CSCs. Here, we review current progress in research related to the multifaceted connections between autophagy modulation and CSCs control using natural products. Overall, we emphasize the importance of understanding the role of autophagy in the maintenance of different CSCs and implications of this connection for the development of new strategies for cancer treatment targeting natural products.
Journal of Clinical Medicine, 2019
Ion channels play important roles in regulating various cellular processes and malignant transfor... more Ion channels play important roles in regulating various cellular processes and malignant transformation. Expressions of some chloride channels have been suggested to be associated with patient survival in gastric cancer (GC). However, little is known about the expression and function of TTYH3, a gene encoding a chloride ion channel, in cancer progression. Here, we comprehensively analyzed the expression of TTYH3 and its clinical outcome in GC using publicly available cancer gene expression and patient survival data through various databases. We examined the differences of TTYH3 expression between cancers and their normal tissues using the Oncomine, UALCAN, and GEO (Gene Expression Omnibus) databases. TTYH3 expression was investigated from immunohistochemistry images using the Human Protein Atlas database. Copy number alterations and mutations of TTYH3 were analyzed using cBioPortal. The co-expression profile of TTYH3 in GC was revealed using Oncomine. The gene ontology and pathway a...
Journal of Clinical Medicine, 2019
C1QBP (Complement Component 1 Q Subcomponent-Binding Protein), a multicompartmental protein, part... more C1QBP (Complement Component 1 Q Subcomponent-Binding Protein), a multicompartmental protein, participates in various cellular processes, including mRNA splicing, ribosome biogenesis, protein synthesis in mitochondria, apoptosis, transcriptional regulation, and infection processes of viruses. The correlation of C1QBP expression with patient survival and molecular function of C1QBP in relation to cancer progression has not been comprehensively studied. Therefore, we sought to systematically investigate the expression of C1QBP to evaluate the change of C1QBP expression and the relationship with patient survival and affected pathways in breast, lung, colon, and bladder cancers as well as lymphoma. Relative expression levels of C1QBP were analyzed using the Oncomine, Gene Expression Across Normal and Tumor Tissue (GENT), and The Cancer Genome Atlas (TCGA) databases. Mutations and copy number alterations in C1QBP were also analyzed using cBioPortal, and subsequently, the relationship betw...
International Journal of Molecular Sciences, 2018
Cytokeratin 19 (KRT19) is a cytoplasmic intermediate filament protein, which is responsible for s... more Cytokeratin 19 (KRT19) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of KRT19 was attenuated in several patients-derived breast cancer tissues and patients with a low expression of KRT19 were significantly correlated with poor prognosis in breast cancer patients. Consistently, highly aggressive and drug-resistant breast cancer patient-derived cancer stem cell-like cells (konkuk university-cancer stem cell-like cell (KU-CSLCs)) displayed higher expression of cancer stem cell (CSC) markers, including ALDH1, CXCR4, and CD133, but a much lower expression of KRT19 than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of KRT19 in MDA-MB231 cells led to an enhancement of cancer properties, such as cell proliferation, sphere formation, migration, and drug resistance, while the overexpression of KRT19 in KU-CSLCs resulted in the significant attenuation of cancer properties. KRT19 regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers (ALDH1, CXCR4, and CD133), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of KRT19 expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment.
Breast Cancer Research, 2019
Background: Epithelial-mesenchymal transition (EMT) occurs in the tumor microenvironment and pres... more Background: Epithelial-mesenchymal transition (EMT) occurs in the tumor microenvironment and presents an important mechanism of tumor cell intravasation, stemness acquisition, and metastasis. During metastasis, tumor cells enter the circulation to gain access to distant tissues, but how this fluid microenvironment influences cancer cell biology is poorly understood. Methods and results: Here, we present both in vivo and in vitro evidence that EMT-like transition also occurs in circulating tumor cells (CTCs) as a result of hydrodynamic shear stress (+SS), which promotes conversion of CD24 middle /CD44 high /CD133 middle /CXCR4 low /ALDH1 low primary patient epithelial tumor cells into specific high sphere-forming CD24 low /CD44 low /CD133 high /CXCR4 high /ALDH1 high cancer stem-like cells (CSLCs) or tumor-initiating cells (TICs) with elevated tumor progression and metastasis capacity in vitro and in vivo. We demonstrate that conversion of CSLCs/TICs from epithelial tumor cells via +SS is dependent on reactive oxygen species (ROS)/nitric oxide (NO) generation, and suppression of extracellular signal-related kinase (ERK)/glycogen synthase kinase (GSK) 3β, a mechanism similar to that operating in embryonic stem cells to prevent their differentiation while promoting self-renewal. Conclusion: Fluid shear stress experienced during systemic circulation of human breast tumor cells can lead to specific acquisition of mesenchymal stem cell (MSC)-like potential that promotes EMT, mesenchymal-epithelial transition, and metastasis to distant organs. Our data revealed that biomechanical forces appeared to be important microenvironmental factors that not only drive hematopoietic development but also lead to acquisition of CSLCs/ TIC potential in cancer metastasis. Our data highlight that +SS is a critical factor that promotes the conversion of CTCs into distinct TICs in blood circulation by endowing plasticity to these cells and by maintaining their selfrenewal signaling pathways.
International journal of molecular sciences, Jan 2, 2018
Influenza virus remains a major health concern worldwide, and there have been continuous efforts ... more Influenza virus remains a major health concern worldwide, and there have been continuous efforts to develop effective antivirals despite the use of annual vaccination programs. The purpose of this study was to determine the anti-influenza activity of Bax inhibitor-1 (). Madin-Darby Canine Kidney (MDCK) cells expressing wild typeand a non-functionalmutant,(with the C-terminal 14 amino acids deleted) were prepared and infected with A/PR/8/34 influenza virus.overexpression led to the suppression of virus-induced cell death and virus production compared to control Mock oroverexpression. In contrast to-overexpressing cells,-overexpressing cells exhibited markedly reduced virus-induced expression of several viral genes, accompanied by a substantial decrease in ROS production. We found that treatment with a ROS scavenging agent,-acetyl cysteine (NAC), led to a dramatic decrease in virus production and viral gene expression in control MDCK and∆C-overexpressing cells. In contrast, NAC treatm...
International journal of molecular sciences, Jan 17, 2017
Inadequate or excessive nutrient consumption leads to oxidative stress, which may disrupt oxidati... more Inadequate or excessive nutrient consumption leads to oxidative stress, which may disrupt oxidative homeostasis, activate a cascade of molecular pathways, and alter the metabolic status of various tissues. Several foods and consumption patterns have been associated with various cancers and approximately 30-35% of the cancer cases are correlated with overnutrition or malnutrition. However, several contradictory studies are available regarding the association between diet and cancer risk, which remains to be elucidated. Concurrently, oxidative stress is a crucial factor for cancer progression and therapy. Nutritional oxidative stress may be induced by an imbalance between antioxidant defense and pro-oxidant load due to inadequate or excess nutrient supply. Oxidative stress is a physiological state where high levels of reactive oxygen species (ROS) and free radicals are generated. Several signaling pathways associated with carcinogenesis can additionally control ROS generation and regu...
International journal of molecular sciences, Jan 12, 2017
Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer... more Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer drug for various cancers, but the synergistic anti-cancer effect of VPA and doxorubicin (DOX) combination treatment and its potential underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC and identify a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VP...
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Papers by Subbroto K Saha