Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Yoon Suk Kim
{"title":"Gefitinib induces anoikis in cervical cancer cells.","authors":"Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Yoon Suk Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers. However, the therapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimed to explore whether gefitinib can be used to treat cervical cancer and elucidate the underlying mechanisms. Results showed that gefitinib induced a caspase-dependent apoptosis of HeLa cells, which consequently became round and detached from the surface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression of p-FAK, integrin β1 and E-cadherin, which are important in cell-extracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells in suspension, leading to poly (ADP-ribose) polymerase cleavage, a hallmark of apoptosis. It also induced detachment-induced apoptosis (anoikis) in C33A cells, another cervical cancer cell line. Taken together, these results suggest that gefitinib triggers anoikis in cervical cancer cells. Our findings may serve as a basis for broadening the range of anticancer drugs used to treat cervical cancer. [BMB Reports 2024; 57(2): 104-109].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10910092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-31DOI: 10.5483/BMBRep.2023-0239
Yunji Kim, D. Kang, Ga-Eun Choi, Sang Dae Kim, Sun-Ja Yang, Hyosang Kim, D. You, Choung Soo Kim, N. Suh
{"title":"Therapeutic potential of BMSC-conditioned medium in an in vitro model of renal fibrosis using the RPTEC/TERT1 cell line","authors":"Yunji Kim, D. Kang, Ga-Eun Choi, Sang Dae Kim, Sun-Ja Yang, Hyosang Kim, D. You, Choung Soo Kim, N. Suh","doi":"10.5483/BMBRep.2023-0239","DOIUrl":"https://doi.org/10.5483/BMBRep.2023-0239","url":null,"abstract":"We investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell-conditioned medium (BMSC-CM) on immortalized renal proximal tubule epithelial cells (RPTEC/TERT1) in a fibrotic environment. To replicate the increased stiffness characteristic of kidneys in chronic kidney disease, we utilized polyacrylamide gel platforms. A stiff matrix was shown to increase α-smooth muscle actin (α-SMA) levels, indicating fibrogenic activation in RPTEC/TERT1 cells. Interestingly, treatment with BMSC-CM resulted in significant reductions in the levels of fibrotic markers (α-SMA and vimentin) and increases in the levels of the epithelial marker E-cadherin and aquaporin 7, particularly under stiff conditions. Furthermore, BMSC-CM modified microRNA (miRNA) expression and reduced oxidative stress levels in these cells. Our findings suggest that BMSC-CM can modulate cellular morphology, miRNA expression, and oxidative stress in RPTEC/TERT1 cells, highlighting its therapeutic potential in fibrotic kidney disease.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140474970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-26DOI: 10.5483/bmbrep.2023-0225
Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Y. Kim
{"title":"Gefitinib induces anoikis in cervical cancer cells","authors":"Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Y. Kim","doi":"10.5483/bmbrep.2023-0225","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0225","url":null,"abstract":"","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139593506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-18DOI: 10.5483/bmbrep.2023-0210
Jong Hee Kim, Jihyeon Yu, Jin Young Kim, Yong Jin Park, Sangsu Bae, Kwon Kyoo Kang, Yu-Jin Jung
{"title":"Phenotypic characterization of pre-harvest sprouting resistance mutants generated by the CRISPR/Cas9-geminiviral replicon system in rice","authors":"Jong Hee Kim, Jihyeon Yu, Jin Young Kim, Yong Jin Park, Sangsu Bae, Kwon Kyoo Kang, Yu-Jin Jung","doi":"10.5483/bmbrep.2023-0210","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0210","url":null,"abstract":"","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139526584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0221
Chul-Sung Park, Omer Habib, Younsu Lee, J. Hur
{"title":"Applications of CRISPR technologies to the development of gene and cell therapy.","authors":"Chul-Sung Park, Omer Habib, Younsu Lee, J. Hur","doi":"10.5483/bmbrep.2023-0221","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0221","url":null,"abstract":"Advancements in gene and cell therapy have resulted in novel therapeutics for diseases previously considered incurable or challenging to treat. Among the various contributing technologies, genome editing stands out as one of the most crucial for the progress in gene and cell therapy. The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the subsequent evolution of genetic engineering technology have markedly expanded the field of target-specific gene editing. Originally studied in the immune systems of bacteria and archaea, the CRISPR system has demonstrated wide applicability to effective genome editing of various biological systems including human cells. The development of CRISPR-based base editing has enabled directional cytosine-tothymine and adenine-to-guanine substitutions of select DNA bases at the target locus. Subsequent advances in prime editing further elevated the flexibility of the edit multiple consecutive bases to desired sequences. The recent CRISPR technologies also have been actively utilized for the development of in vivo and ex vivo gene and cell therapies. We anticipate that the medical applications of CRISPR will rapidly progress to provide unprecedented possibilities to develop novel therapeutics towards various diseases.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-04DOI: 10.5483/BMBRep.2023-0187
Y. Kim, Baeki E Kang, Karim Gariani, Joanna Gariani, Junguee Lee, Hyun-Jin Kim, Chang-Woo Lee, Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu
{"title":"Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair","authors":"Y. Kim, Baeki E Kang, Karim Gariani, Joanna Gariani, Junguee Lee, Hyun-Jin Kim, Chang-Woo Lee, Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu","doi":"10.5483/BMBRep.2023-0187","DOIUrl":"https://doi.org/10.5483/BMBRep.2023-0187","url":null,"abstract":"The mammalian sirtuin family (SIRT1–SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140514107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0248
Ju-Chan Park, Sangsu Bae
{"title":"Current status of genome editing technologies: special issue of BMB Reports in 2024.","authors":"Ju-Chan Park, Sangsu Bae","doi":"10.5483/bmbrep.2023-0248","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0248","url":null,"abstract":"Since the identification of DNA as a genetic material, manipulating DNA in various organisms has been a long standing dream of humanity. In pursuit of this objective, technologies to edit genome have been extensively developed over the recent decades. The emergence of zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems enabled site-specific DNA cleavage in a programmable manner. Furthermore, the advent of base editors (BEs) and prime editors (PEs) has enabled base conversion and insertion/deletion with a high accuracy. In addition to the editing of genomic DNA in the nucleus, attempts to manipulate circular DNAs in organelle are currently ongoing. These technologies are bringing major progress in diverse fields including the engineering of cells, livestock, and plants as well as therapeutic gene correction in humans. In this special issue, we aim to cover the recent advances in genome editing technology and its applications in therapeutics, breed improvement in plants and livestock, RNA recording, and protein evolution.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0224
Kayeong Lim
{"title":"Mitochondrial genome editing: strategies, challenges, and applications.","authors":"Kayeong Lim","doi":"10.5483/bmbrep.2023-0224","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0224","url":null,"abstract":"Mitochondrial DNA (mtDNA), a multicopy genome found in mitochondria, is crucial for oxidative phosphorylation. Mutations in mtDNA can lead to severe mitochondrial dysfunction in tissues and organs with high energy demand. MtDNA mutations are closely associated with mitochondrial and age-related disease. To better understand the functional role of mtDNA and work toward developing therapeutics, it is essential to advance technology that is capable of manipulating the mitochondrial genome. This review discusses ongoing efforts in mitochondrial genome editing with mtDNA nucleases and base editors, including the tools, delivery strategies, and applications. Future advances in mitochondrial genome editing to address challenges regarding their efficiency and specificity can achieve the promise of therapeutic genome editing.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondrial genome editing: strategies, challenges, and applications.","authors":"Kayeong Lim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mitochondrial DNA (mtDNA), a multicopy genome found in mitochondria, is crucial for oxidative phosphorylation. Mutations in mtDNA can lead to severe mitochondrial dysfunction in tissues and organs with high energy demand. MtDNA mutations are closely associated with mitochondrial and age-related disease. To better understand the functional role of mtDNA and work toward developing therapeutics, it is essential to advance technology that is capable of manipulating the mitochondrial genome. This review discusses ongoing efforts in mitochondrial genome editing with mtDNA nucleases and base editors, including the tools, delivery strategies, and applications. Future advances in mitochondrial genome editing to address challenges regarding their efficiency and specificity can achieve the promise of therapeutic genome editing. [BMB Reports 2024; 57(1): 19-29].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances in genome engineering by CRISPR technology.","authors":"Youngsik Lee, Yeounsun Oh, Seung Hwan Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Due to the development of CRISPR technology, the era of effective editing of target genes has arrived. However, the offtarget problem that occurs when recognizing target DNA due to the inherent nature of CRISPR components remains the biggest task to be overcome in the future. In this review, the principle of inducing such unintended off-target editing is analyzed from the structural aspect of CRISPR, and the methodology that has been developed to reduce off-target editing until now is summarized. [BMB Reports 2024; 57(1): 12-18].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}