Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(2)
Published: Feb. 1, 2022
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)
Published: March 29, 2021
Abstract Currently, pyroptosis has received more and attention because of its association with innate immunity disease. The research scope expanded the discovery gasdermin family. A great deal evidence shows that can affect development tumors. relationship between tumors is diverse in different tissues genetic backgrounds. In this review, we provide basic knowledge pyroptosis, explain tumors, focus on significance tumor treatment. addition, further summarize possibility as a potential treatment strategy describe side effects radiotherapy chemotherapy caused by pyroptosis. brief, double-edged sword for rational use dual effect will help us explore formation ideas patients to develop new drugs based
Language: Английский
Citations
1548
Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)
Published: May 27, 2020
Gastric cancer is a deadly disease and remains the third leading cause of cancer-related death worldwide. The 5-year overall survival rate patients with early-stage localized gastric more than 60%, whereas that distant metastasis less 5%. Surgical resection best option for cancer, while chemotherapy mainly used in middle advanced stages this disease, despite frequently reported treatment failure due to resistance. Therefore, there an unmet medical need identifying new biomarkers early diagnosis proper management patients, achieve response treatment. Long non-coding RNAs (lncRNAs) body fluids have attracted widespread attention as screening, diagnosis, treatment, prognosis, responses drugs high specificity sensitivity. In present review, we focus on clinical potential lncRNAs liquid biopsies prognosis cancer. We also comprehensively discuss roles their molecular mechanisms chemoresistance well therapeutic targets precision medicine.
Language: Английский
Citations
264
Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 138, P. 111528 - 111528
Published: March 23, 2021
MicroRNAs (miRNAs) are a group of small non-coding RNAs that post-transcriptionally control expression genes by targeting mRNAs. miRNA alterations partake in the establishment and progression different types human cancer. Consequently, profiling cancers has correlations with cancer detection, staging, progression, response to therapies. Particularly, amplification, deletion, abnormal pattern epigenetic factors transcriptional mediate regulation primary frequently change landscape Indeed, changes quantity quality miRNAs associated initiation cancer, its metastasis. Additionally, been used categorize can affect oncogenic pathways Here, we discuss several circulating signatures, their profiles impacts on cellular processes.
Language: Английский
Citations
242
Cancer Communications, Journal Year: 2022, Volume and Issue: 42(2), P. 117 - 140
Published: Jan. 12, 2022
Abstract With the development of proteomics and epigenetics, a large number RNA‐binding proteins (RBPs) have been discovered in recent years, interaction between long non‐coding RNAs (lncRNAs) RBPs has also received increasing attention. It is extremely important to conduct in‐depth research on lncRNA‐RBP network, especially context its role occurrence cancer. Increasing evidence demonstrated that interactions play vital cancer progression; therefore, targeting these could provide new insights for drug discovery. In this review, we discussed how lncRNAs can interact with regulate their localization, modification, stability, activity effects transport, transcription, localization lncRNAs. Moreover, explored regulation influence lncRNAs, RBPs, downstream pathways are related development, such as N6‐methyladenosine (m6A) modification addition, network regulates cell phenotypes, proliferation, apoptosis, metastasis, resistance, immunity, tumor environment, metabolism. Furthermore, summarized therapeutic strategies target network. Although treatments still experimental stage various theories processes being studied, believe may ideas treatment.
Language: Английский
Citations
174
Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)
Published: March 12, 2022
Epithelial-to-mesenchymal transition (EMT) is a process linked to metastasis and drug resistance with non-coding RNAs (ncRNAs) playing pivotal roles. We previously showed that miR-100 miR-125b, embedded within the third intron of ncRNA host gene MIR100HG, confer cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in colorectal cancer (CRC). However, whether MIR100HG transcript itself has role cetuximab or EMT unknown.The correlation between was analyzed by curating public CRC data repositories. The biological roles EMT, were determined both vitro vivo. expression patterns hnRNPA2B1 TCF7L2 specimens from patients who progressed on metastatic disease RNAscope immunohistochemical staining.The strongly correlated markers acted as positive regulator EMT. sustained facilitated invasion cells identified binding partner MIR100HG. Mechanistically, maintained mRNA stability TCF7L2, major transcriptional coactivator Wnt/β-catenin signaling, interacting hnRNPA2B1. recognized N6-methyladenosine (m6A) site presence turn, activated transcription, forming feed forward regulatory loop. MIR100HG/hnRNPA2B1/TCF7L2 axis augmented either developed local distant had progression associated resistance.MIR100HG interact control activity Wnt signaling via regulation stability. Our findings potent inducer may contribute activation feedback
Language: Английский
Citations
131
Clinical and Translational Medicine, Journal Year: 2021, Volume and Issue: 11(6)
Published: June 1, 2021
Abstract Background Bone metastasis is the leading cause of tumor‐related death in prostate cancer (PCa) patients. Long noncoding RNAs (lncRNAs) have been well documented to be involved progression multiple cancers. Nevertheless, role lncRNAs PCa bone remains largely unclear. Methods The expression cancer‐associated transcripts was analyzed published datasets and further verified clinical samples cell lines by RT‐qPCR situ hybridization assays. Colony formation assay, MTT cycle analysis, EdU Transwell migration invasion assays, wound healing vivo experiments were carried out investigate function transcript 6 ( PCAT6 ) tumor growth PCa. Bioinformatic RNA pull‐down, RIP assays conducted identify proteins binding potential targets . therapeutic targeting antisense oligonucleotides (ASO) explored Results upregulated tissues with increased predicted poor prognosis Functional found that knockdown significantly inhibited invasion, migration, proliferation vitro , as Mechanistically, METTL3 ‐mediated m A modification contributed upregulation an IGF2BP2 ‐dependent manner. Furthermore, IGF1R enhancing mRNA stability through / RNA‐protein three‐dimensional complex. Importantly, inhibition ASO showed against Finally, correlation demonstrated cells. Conclusions Our study uncovers a novel molecular mechanism which A‐induced axis promotes growth, suggesting may serve promising prognostic marker target bone‐metastatic
Language: Английский
Citations
119
Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)
Published: March 7, 2022
Abstract Background Esophageal squamous cell carcinoma (ESCC) is a common invasive malignancy worldwide with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been reported to be involved in cancer development. However, lncRNAs that are functional ESCC and the underlying molecular mechanisms remain largely unknown. Methods Transcriptomic analysis was performed identify dysregulated tissue samples. The high expression LINC00680 validated by RT-qPCR, oncogenic functions investigated proliferation, colony formation, migration invasion assays cells vitro xenografts derived from mice. RNA-seq, competitive endogenous RNA (ceRNA) network analysis, luciferase reporter were carried out target genes microRNAs (miRNAs) bound LINC00680. Antisense oligonucleotides (ASOs) used for vivo treatment. Results Transcriptome profiling revealed large number tissues. Notably, highly expressed, upregulation associated tumor size, advanced stage, prognosis. Functionally, knockdown restrained migration, inhibited growth vivo. Mechanistically, found act as ceRNA sponging miR-423-5p regulate PAK6 (p21-activated kinase 6) cells. viability motility inhibition induced significantly reversed upon restoration inhibition. Furthermore, ASO targeting substantially suppressed both Conclusions An lncRNA, LINC00680, identified ESCC, which promote ESCC. LINC00680/miR-423-5p/PAK6 axis may serve promising diagnostic prognostic biomarkers therapeutic targets
Language: Английский
Citations
97
Journal of Education Health and Sport, Journal Year: 2022, Volume and Issue: 12(8), P. 730 - 926
Published: Aug. 23, 2022
The book is intended for students studying medical and biological specialties. CHAPTER I. EPIGENETICS INTRODUCTION science of epigenetics looks at the mechanisms molecular modifications histones DNA that can regulate gene activity without affecting nucleotide sequences in molecule. Recognized epigenetic regulators are methylation, post-translational histones, non-coding RNAs (nkRNAs). One most important differences between eukaryotic cells prokaryotes presence a complex nucleo-protein chromatin eukaryotes. It this form molecule stored our cells. On one hand, structural organization provides compact arrangement cell nucleus. other directly involved process regulating expression. At same time, nucleosome depicted Fig. 1 (a functional unit chromatin) considered as key component processes nucleus 8 histone proteins (octamers). consists two copies each H2A, H2B, H3 H4. chain, which includes 147 nucleotides, folds 1.65 times around octamer histones. nucleosomes arranged linear array along "beads on string". linker section connecting adjacent (transcriptionally inactive) sealed with H1-histone protein. length 30 nm. Moreover, site beginning transcription usually located inside nucleosome. Consequently, serves repressor, preventing initiation transcription. That is, total repression genes. In contrast, becomes possible result remodeling factors enable "dismantling" or otherwise alter their structure organization. Thus, (inactivation) genes begins wrapping nucleosome, liberation from (activation) involves freeing binding to unfolding by (Lorch Y., Kornberg R. D., 2017). Thanks mechanism, selective expression only those needed given time tissue possible. should be emphasized extends not transcription, but also associated molecule, such replication, mitotic division, repair double-strand breaks, maintenance telomeres. control various physiological pathological corresponding changing availability systems chromatin. scope application research methods rapidly expanding. Currently, we witnessing active introduction approaches field practical medicine aimed diagnosing treating dangerous human diseases. II. TRANSCRIPTION FACTORS For first existence was revealed basis discovery made it establish vitro purified RNA polymerase-II initiate template extract (Weil P. A. et al., 1979). Further fractionation identification general (GTF) required has identified similar rats, Drosophila, yeast substantiated assumption GTFs indeed "common" necessary transcribed polymerase highly conserved number organisms (Matsui T. 1980). We mention II because type enzyme ability synthesize mRNA. Whereas I responsible synthesis pro-rRNA, III tRNA RNAs. Meanwhile, regulation eukaryotes quite complex, since depends complexes (Burns L. G., Peterson C. L., 1997) covalent modification (Natsume-Kitatani Mamitsuka H., 2016). initiation, immediate target GTF well-defined promo zone gene. promotra eukaryotes, main elements regulatory distinguished. (bark promoter, see 2.1) attributed assembling (PIC), including TATA sequence above start (TSS ), an initiating (Inr) covering site. Promoters may include unit, initiator (Inr), both (Hampsey M., 1998). A third major element, downstream promoter element (DPE), originally described Drosophila about p.p. below TSS. DPE appears function conjunction Inr factor TFIID non-TATA promoters. According current research, cellular (main) promoters multicellular contain short nucleotides called cow (motifs) (e.g., block, lower (DPE)) recruit through common mechanism (Dreos 2021). authors report classes Inr+DPE present genome humans structurally other, different species organisms. studied box, box found 10-20% cortical Therefore, sequence, name known elements, include: BRE, MTE, TST sequences. BRE (TFIIB recognition element) motifs either (BREu) (BREd) box. TBP, demonstrate high levels conservatism range archaebacteria (Kadonaga J. T., 2012). doing so, BREu well BREd have positive negative effects activity. core (DPE) detected analysis Drosophila. MTE (motif ten element), front DPE, overrepresented "motif 10" then discovered, promoter. exhibit humans, appear recognized subunits TFIID, TAF resemble structure. turn, TCT regulates ribosomal protein humans. Although there no universal all promoters, concept nuclear defined minimum stretch sufficient accurately 2012; Haberle V., Stark A., 2018). noted results modern will constantly supplement list new components example, DNA-replicatedrelated (DRE), Ohler 1,6 7 (Danino Y. M. 2015; authors, bark transformed course evolution. Due this, modulated composition elements. Such modulation achieved emergence combinations additional level realized. To summarize facts, initiated specific position, Transcription Initiation Site (TSS), 5' end TSS embedded spanning 50 base pairs platform related (GTFs). Regulatory low basal activity, further activated, generally more distally enhancers (discussed below). Enhancers bind factors, cofactors, enhance III. CELL SIGNALING PATHWAYS organism, work regulated large signals. These signals formed organism itself, reflecting needs living (metabolic state, stages development, differentiation, reproduction), reaction external environment. implementation these encompasses biochemical lead cell's perception signal response. something receptor, turn response signal. receptor recognizes signal, interprets specificity translates into intracellular signaling molecules, cascade phosphorylation, pathways. soon (ligand) binds its – complementary transmembrane cell. Growth hormones, cytokines, neurotransmitters, extracellular matrix, etc. chemical nature ligands diverse, small molecules lipids (prostaglandins, steroid hormones), (for peptide cytokines chemokines, growth factors)., polymers sugars β-glucan zymosan) proteoglycans), nucleic acids, Binding ligand induces conformational changes translated activating cascades secondary messengers (kinases, phosphatases, GTPases, ions cAMP, cGMP, diacylglycerol, etc.). message transmitted membrane nucleus, where expression, subsequent translation targeting organelles triggered. There types receptors (transmembrane) receptors. Membrane plasma separate domain ligand, hydrophobic nature, cytoplasmic domain. Cell surface divided G-protein-bound receptors, tyrosine kinase-bound ionotropic When binds, undergo activate enzymatic domain, kinases, phosphatases adapter proteins. covalently bound capable producing transmission. Intracellular (estrogen glucocorticoid progesterone retinoic acid thyroid hormone etc.), membranes (mitochondria, endoplasmic reticulum Golgi apparatus). information received receptor) targets. All path transmission However, certain set effector proteins, enzymes substrates implement pathway (signaling cascade). Recently, however, been growing evidence themselves play extremely role signaling, theso-called scaffold ("platform proteins", adaptor proteins), coordinate assembly multicomponent complexes. Scaffold several single thereby modulating efficiency bringing closer together, direct flow cell, activating, coordinating events networks (Skovorodnikova P.A. literature, described, cover wide functions. This group three categories (Fig. 1): simple functionally dependent (adaptors), larger multi-domain designed (scaffold⁄anchoring proteins) specialized localizing proteins-components pathways (docking ( Buday Tompa P, 2010) platforms increases selectivity pathway, allows formation feedback. e ultimate ultimately allow resulting converted change (Brivanlou Darnell E., 2002). Most eventually activation repressors sequence. Eukaryotic like takes place cytoplasm. Signal multifactorial system, based nodular special cascades. none isolation. interaction inevitable complexes, when system perceives combination stimuli (hormones, pathogenic ligands), preserves accuracy (Saini N., Sarin relatively development mammals Combinations action determine decisions fate differentiation ontogenesis (Li R., Elowitz M.V., 2019; de Roo Staal F. 2020) malignancy (Dreesen O., Brivanlou A.N., 2007; Skovorodnikova Consider some medically important. IV. MOLECULAR BIOLOGY OF THE TUMOR: MECHANISMS INITIATION, PROMOTION AND PROGRESSION Tumor diseases occupy leading place, terms morbidity mortality. despite advances study genetic patterns, many unresolved questions remain. spectrum markers makes diagnose, predict course, degree malignancy, rate tumor progression therapy. occur characterized stability, they dynamic profile - appearance clones properties. heterogeneity simultaneously complicates strategy managing patients, creating prerequisites characteristics
Language: Английский
Citations
96
Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 29, 2025
Abstract Long noncoding RNAs (lncRNAs) are key regulators during gastric cancer (GC) development and may be viable treatment targets. In the present study, we showed that expression of long intergenic RNA 01016 (LINC01016) is significantly higher in GC tissues with lymph node metastasis (LNM) than those without LNM. LINC01016 overexpression predicts a poorer relapse-free survival (RFS) overall (OS). Furthermore, found activated by transcriptional factor SP-1 contributes to overt promotion cell migratory ability. EIF4A3 was identified as binding partner pull-down assay, mass spectrometry western blot. We determined can blocks MMP9 mRNA, thereby inhibiting EIF4A3-mediated nonsense-mediated decay (NMD), increasing mRNA level protein levels promote tumor progression. or LINC01016-mediated EIF4A3/MMP9 potential therapeutic targets for patients GC.
Language: Английский
Citations
2
Food and Chemical Toxicology, Journal Year: 2021, Volume and Issue: 157, P. 112576 - 112576
Published: Sept. 27, 2021
Language: Английский
Citations
96