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Prognostic role of EGR1 in breast cancer: a systematic review
( Subbroto Kumar Saha ),( S. M. Riazul Islam ),( Tripti Saha ),( Afsana Nishat ),( Polash Kumar Biswas ),( Minchan Gil ),( Lewis Nkenyereye ),( Shaker El-sappagh ),( Saiful Islam ),( Ssang-goo Cho ) 생화학분자생물학회 2021 BMB Reports Vol.54 No.10
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]
Saha, Subbroto Kumar,Kim, Kyeongseok,Yang, Gwang-Mo,Choi, Hye Yeon,Cho, Ssang-Goo MDPI AG 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.5
<P>Cytokeratin 19 (<I>KRT19</I>) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, <I>KRT19</I> is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of <I>KRT19</I> as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of <I>KRT19</I> in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of <I>KRT19</I> was attenuated in several patients-derived breast cancer tissues and patients with a low expression of <I>KRT19</I> 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 <I>ALDH1</I>, <I>CXCR4</I>, and <I>CD133</I>, but a much lower expression of <I>KRT19</I> than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of <I>KRT19</I> 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 <I>KRT19</I> in KU-CSLCs resulted in the significant attenuation of cancer properties. <I>KRT19</I> regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers (<I>ALDH1</I>, <I>CXCR4</I>, and <I>CD133</I>), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of <I>KRT19</I> expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment. </P>
Saha, Subbroto Kumar,Yin, Yingfu,Kim, Kyeongseok,Yang, Gwang-Mo,Abdal Dayem, Ahmed,Choi, Hye Yeon,Cho, Ssang-Goo MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.5
<P>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 VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.</P>
( Hye Yeon Choi ),( Subbroto Kumar Saha ),( Kyeong Seok Kim ),( Sang Su Kim ),( Gwang Mo Yang ),( Bong Woo Kim ),( Jin Hoi Kim ),( Ssang Goo Cho ) 생화학분자생물학회 2015 BMB Reports Vol.48 No.2
G protein-coupled receptors (GPCRs) are a large class of transmembrane receptors categorized into five distinct families: rhodopsin, secretin, adhesion, glutamate, and frizzled. They bind and regulate 80% of all hormones and account for 20-50% of the pharmaceuticals currently on the market. Hundreds of GPCRs integrate and coordinate the functions of individual cells, mediating signaling between various organs. GPCRs are crucial players in tumor progression, adipogenesis, and inflammation. Several studies have also confirmed their central roles in embryonic development and stem cell maintenance. Recently, GPCRs have emerged as key players in the regulation of cell survival, proliferation, migration, and self-renewal in pluripotent (PSCs) and cancer stem cells (CSCs). Our study and other reports have revealed that the expression of many GPCRs is modulated during the generation of induced PSCs (iPSCs) or CSCs as well as during CSC sphere formation. These GPCRs may have crucial roles in the regulation of selfrenewal and other biological properties of iPSCs and CSCs. This review addresses the current understanding of the role of GPCRs in stem cell maintenance and somatic reprogramming to PSCs or CSCs. [BMB Reports 2015; 48(2): 68-80]
Antibacterial and phytochemical properties of Aphanamixis polystachya essential oil
Rahman, Md. Shahedur,Ahad, Abir,Saha, Subbroto Kumar,Hong, Jongki,Kim, Ki-Hyun The Korean Society of Analytical Science 2017 분석과학 Vol.30 No.3
Now a day's rise of new antibiotic resistant bacterial strains is a global threat. Ethnic people of India have been employing Aphanamixis polystachya (Wall.) R. Parker wood extract in healing cancerous wounds. The aim of this study was to evaluate the antimicrobial activity and to identify the medicinally potent chemicals in the essential oil extract of A. polystachya. The antibacterial properties of various organic extracts were evaluated against a range of bacteria (gram-positive and gram-negative bacteria) based on the disc diffusion method and GC-MS based analysis for finding active oil extract components. All extracts of A. polystachya leaves showed potential antibacterial activity, notably ethyl acetate, while petroleum ether extracts revealed highly sensitive activity against all tested bacteria (zones of inhibition ranging from 8.83 to 11.23 mm). In addition, the petroleum ether extract had the lowest MIC value (32 to $256{\mu}g/mL$) against E. coli, S. lutea, X. campestris, and B. subtilis bacteria. The major compounds detected in oil [${\beta}$-elemene (16.04 %), ${\beta}$-eudesmol (12.78 %), ${\beta}$-caryophyllene (19.37 %), ${\beta}$-selinene (11.32 %), elemol (5.76 %), and ${\alpha}$-humulene (5.68 %)] are expected to be responsible for the potent antimicrobial activity. The results of this study offer valuable insights into the potent role of A. polystachya essential oil extract in pharmaceutical and antibiotic research.
Kawser Hossain, Mohammed,Abdal Dayem, Ahmed,Han, Jihae,Kumar Saha, Subbroto,Yang, Gwang-Mo,Choi, Hye Yeon,Cho, Ssang-Goo MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.2
<P>Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.</P>
Dayem, Ahmed Abdal,Kim, BongWoo,Gurunathan, Sangiliyandi,Choi, Hye Yeon,Yang, Gwangmo,Saha, Subbroto Kumar,Han, Dawoon,Han, Jihae,Kim, Kyeongseok,Kim, Jin-Hoi,Cho, Ssang-Goo Wiley 2014 Biotechnology Journal Vol.9 No.7
<P>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 AgNPs-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.</P>