LncRNAs Dotaz Zobrazit nápovědu
The adaptive immune system is responsible for generating immunological response and immunological memory. Regulation of adaptive immunity including B cell and T cell biology was mainly understood from the protein and microRNA perspective. However, long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs (ncRNAs) that influence key factors in lymphocyte biology such as NOTCH, PAX5, MYC and EZH2. LncRNAs were described to modulate lymphocyte activation by regulating pathways such as NFAT, NFκB, MYC, interferon and TCR/BCR signalling (NRON, NKILA, BCALM, GAS5, PVT1), and cell effector functions (IFNG-AS1, TH2-LCR). Here we review lncRNA involvement in adaptive immunity and the implications for autoimmune diseases (multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis) and T/B cell leukaemias and lymphomas (CLL, MCL, DLBCL, T-ALL). It is becoming clear that lncRNAs are important in adaptive immune response and provide new insights into its orchestration.
- Klíčová slova
- Adaptive immunity, Autoimmune diseases, B cell, B/T cell activation, Leukaemia, LncRNAs, Lymphocyte development, Lymphoma, T cell, T cell polarization,
- MeSH
- adaptivní imunita genetika MeSH
- aktivace lymfocytů genetika MeSH
- lidé MeSH
- nemoc genetika MeSH
- RNA dlouhá nekódující genetika fyziologie MeSH
- signální transdukce genetika imunologie MeSH
- T-lymfocyty fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující MeSH
MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.
- Klíčová slova
- MYC, autophagy, gene regulatory networks (GRNs), lncRNAs,
- MeSH
- autofagie * MeSH
- genové regulační sítě * MeSH
- lidé MeSH
- protoonkogenní proteiny c-myc genetika metabolismus MeSH
- regulace genové exprese u nádorů * MeSH
- RNA dlouhá nekódující genetika metabolismus MeSH
- RNA nádorová genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- MYC protein, human MeSH Prohlížeč
- protoonkogenní proteiny c-myc MeSH
- RNA dlouhá nekódující MeSH
- RNA nádorová MeSH
Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.
- Klíčová slova
- LncRNAs, autophagy, cancer stem cells (CSCs), haematological malignancies, solid cancers, tumour microenvironment,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Although colorectal cancer (CRC) is the third most frequent cause of cancer related death in Europe, clinically relevant biomarkers for therapy guidance and prognosis are insufficiently reliable. Long non-coding RNAs (lncRNAs) are RNAs over 200 nucleotides long that are not translated into proteins but can influence biological processes. There is emerging evidence for their involvement in solid cancer as oncogenes, tumour suppressors or regulators of cell proliferation and metastasis development. The goal of this study was to evaluate the prognostic effect of selected lncRNAs in a retrospective study on CRC patients from the Czech Republic. We used a quantitative PCR approach to measure the expression in paired non-malignant and tumour tissue samples of CRC patients of nine lncRNAs previously shown to be involved in cancer progression-ANRIL, CCAT1, GAS5, linc-ROR, MALAT1, MIR155HG, PCAT1, SPRY4-IT1 and TUG1. Associations between expression and expression ratios and clinical characteristics and survival were assessed by using univariable Cox proportional hazards models, Kaplan-Meier estimations with the Gehan-Wilcoxon test, the Mann-Whitney U test, the Kruskal-Wallis test and Spearman's correlations. A comparison of expression in tumour tissue (TT) and non-malignant mucosa tissue (MT) showed significant upregulation of CCAT1 and linc-ROR in TT (p < 0.001 and p = 0.001, respectively) and downregulation of ANRIL, MIR155HG and MALAT1 (p = 0.001, p = 0.010, p = 0.001, respectively). Linc-ROR was significantly associated with the presence of synchronous metastases (p = 0.033). For individual tissue types, lower MIR155HG expression in TT was correlated with both shorter overall survival (p = 0.008) and shorter disease-free survival (p = 0.040). In MT, expression ratios of CCAT1/ANRIL and CCAT1/MIR155HG were associated with overall survival (p = 0.005 and p = 0.006, respectively). Our results revealed that changes in expression of lncRNAs between MT and TT hold potential to be used as prognostic biomarkers in CRC patients. Moreover, the ratios of CCAT1 to ANRIL and MIR155HG in MT also exhibit potential for prognosis assessment without tumour sampling. Our results also indicate that cancer progression is associated with detrimental system-wide changes in patient tissue, which might govern patient survival even after successful elimination of tumour or cancerous cells.
- Klíčová slova
- CCAT1, MIR155HG, PCAT1, colorectal carcinoma, lncRNA, lncRNA ratio,
- MeSH
- dospělí MeSH
- Kaplanův-Meierův odhad MeSH
- kolorektální nádory diagnóza epidemiologie genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- regulace genové exprese u nádorů * MeSH
- retrospektivní studie MeSH
- RNA dlouhá nekódující genetika MeSH
- senioři MeSH
- upregulace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- nádorové biomarkery MeSH
- RNA dlouhá nekódující MeSH
BACKGROUND: Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of quickly emerging new data regarding the molecular heterogeneity of invasive cancers, far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in the heterogeneity feature of BC. METHODS: In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues. And finally, bio-informatic evaluation has been done. RESULTS: The results of quantitative polymerase chain reaction showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P = 0.0085 and P = 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P = 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with the age at menarche < 14 years compared to patients with the age at menarche 14 (P = 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P = 0.047). And finally, using bio-informatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA zinc finger and BTB domain containing 10 (ZBTB10). CONCLUSION: Altogether, our findings suggest that these lncRNAs with potential oncogenic roles are involved in the pathogenesis of IDC with clinical significance and they may therefore serve as novel markers for the dia-gnosis and treatment of IDC.
- Klíčová slova
- LOC100288637, Prognosis, RP11-48B3, heart failure, invasive ductal breast carcinoma, long non-coding RNA, long noncoding RNAs,
- MeSH
- dospělí MeSH
- duktální karcinom prsu genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prsu genetika MeSH
- prsy metabolismus MeSH
- receptor erbB-2 metabolismus MeSH
- receptory pro estrogeny metabolismus MeSH
- receptory progesteronu metabolismus MeSH
- RNA dlouhá nekódující * MeSH
- senioři MeSH
- signální transdukce MeSH
- výpočetní biologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ERBB2 protein, human MeSH Prohlížeč
- receptor erbB-2 MeSH
- receptory pro estrogeny MeSH
- receptory progesteronu MeSH
- RNA dlouhá nekódující * MeSH
Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides. Due to modern genomic techniques, the involvement of lncRNAs in tumorigenesis has been revealed; however, information concerning lncRNA interplay in multiple myeloma (MM) and plasma cell leukemia (PCL) is virtually absent. Herein, we aimed to identify the lncRNAs involved in MM to PCL progression. We investigated representative datasets of MM and PCL patients using next-generation sequencing. In total, 13 deregulated lncRNAs (p < 0.00025) were identified; four of them were chosen for further validation in an independent set of MM and PCL patients by RT-qPCR. The obtained results proved the significant downregulation of lymphocyte antigen antisense RNA 1 (LY86-AS1) and VIM antisense RNA 1 (VIM-AS1) in PCL compared to MM. Importantly, these two lncRNAs could be involved in the progression of MM into PCL; thus, they could serve as promising novel biomarkers of MM progression.
- Klíčová slova
- biomarkers, disease progression, long non-coding RNA, multiple myeloma, next-generation sequencing, plasma cell leukemia,
- Publikační typ
- časopisecké články MeSH
Renal cell carcinoma (RCC), a prevalent form of renal malignancy, is distinguished by its proclivity for robust tumor proliferation and metastatic dissemination. Long non-coding RNAs (lncRNAs) have emerged as pivotal modulators of gene expression, exerting substantial influence over diverse biological processes, encompassing the intricate landscape of cancer development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), an exemplar among lncRNAs, has been discovered to assume functional responsibilities within the context of RCC. The conspicuous expression of MALAT-1 in RCC cells has been closely linked to the advancement of tumors and an unfavorable prognosis. Experimental evidence has demonstrated the pronounced ability of MALAT-1 to stimulate RCC cell proliferation, migration, and invasion, thereby underscoring its active participation in facilitating the metastatic cascade. Furthermore, MALAT-1 has been implicated in orchestrating angiogenesis, an indispensable process for tumor expansion and metastatic dissemination, through its regulatory influence on pro-angiogenic factor expression. MALAT-1 has also been linked to the evasion of immune surveillance in RCC, as it can regulate the expression of immune checkpoint molecules and modulate the tumor microenvironment. Hence, the potential utility of MALAT-1 as a diagnostic and prognostic biomarker in RCC emerges, warranting further investigation and validation of its clinical significance. This comprehensive review provides an overview of the diverse functional roles exhibited by MALAT-1 in RCC.
- Klíčová slova
- Biomarker, MALAT-1, Renal cell carcinoma, lncRNAs,
- MeSH
- karcinom z renálních buněk * genetika patologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí genetika MeSH
- nádory ledvin * genetika patologie MeSH
- prognóza MeSH
- proliferace buněk genetika MeSH
- RNA dlouhá nekódující * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující * MeSH
BACKGROUND: Cervical cancer as a common urogenital cancer among women has caused significant health problems. Efforts have been made to identify its pathogenic process in order to find targeted ther-apies. Long non-cod-ing ribonucleic acids (lncRNAs) have been shown to regulate several cancer-related pathways and genes that contribute to pathogenesis of human malignancies, includ-ing cervical cancer. In the present review, we searched PubMed, Google scholar, Web of Science and Scopus databases for key words "cervical cancer" or "cervical neoplasm" and "long non-cod-ing RNA" or "lncRNA" (up to December 2017). AIM: To elaborate the role of lncRNAs in cervical cancer. CONCLUSIONS: LncRNAs affect cervical cancer pathogenesis through numerous mechanisms, such as mak-ing scaffolds for assembly of protein complexes, serv-ing as directors to recruit proteins, function-ing as transcriptional enhancers through chromatin remodeling, serv-ing as decoys to free up proteins from chromatin, or revers-ing the effects of other regulatory non-cod-ing RNAs, such as microRNAs. Pathway-based analysis showed that several lncRNAs modulate PI3K/ Akt/ mTOR, Wnt-β catenin and Notch pathways in the process of cervical cancer pathogenesis. In addition, expression of a handful of lncRNAs has been associated with human papilloma virus infection. Identification of lncRNAs that alter cancer-related signal-ing pathways and subsequent expression analysis of these lncRNAs in patients samples would help to design effective targeted ther-apies. Key words: lncRNA - cervical cancer - oncogene - tumor suppressor gene.
- Klíčová slova
- Wnt-β catenin and Notch pathways in the process of cervical cancer pathogenesis. In addition, expression of a handful of lncRNAs has been associated with human papilloma virus infection. Identification of lncRNAs that alter cancer-related signaling pathways and subsequent expression analysis of these lncRNAs in patients samples would help to design effective targeted therapies. Key words: lncRNA - cervical cancer - oncogene - tumor suppressor gene, functioning as transcriptional enhancers through chromatin remodeling, or reversing the effects of other regulatory non-coding RNAs, serving as decoys to free up proteins from chromatin, serving as directors to recruit proteins, such as making scaffolds for assembly of protein complexes, such as microRNAs. Pathway-based analysis showed that several lncRNAs modulate PI3K/ Akt/ mTOR, “cervical cancer” or “cervical neoplasm” and “long non-coding RNA” or “lncRNA” (up to December 2017). Aim: To elaborate the role of lncRNAs in cervical cancer. Conclusions: LncRNAs affect cervical cancer pathogenesis through numerous mechanisms,
- MeSH
- epitelo-mezenchymální tranzice MeSH
- imunitní únik MeSH
- infekce papilomavirem genetika MeSH
- lidé MeSH
- nádory děložního čípku genetika imunologie metabolismus MeSH
- RNA dlouhá nekódující * MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující * MeSH
Colorectal cancer (CRC) is the second most prevalent cancer type worldwide, which highlights the urgent need for non-invasive biomarkers for its early detection and improved prognosis. We aimed to investigate the patterns of long non-coding RNAs (lncRNAs) in small extracellular vesicles (sEVs) collected from low-volume blood serum specimens of CRC patients, focusing on their potential as diagnostic biomarkers. Our research comprised two phases: an initial exploratory phase involving RNA sequencing of sEVs from 76 CRC patients and 29 healthy controls, and a subsequent validation phase with a larger cohort of 159 CRC patients and 138 healthy controls. Techniques such as dynamic light scattering, transmission electron microscopy, and Western blotting were utilized for sEV characterization. Optimized protocol for sEV purification, RNA isolation and preamplification was applied to successfully sequence the RNA content of sEVs and validate the results by RT-qPCR. We successfully isolated sEVs from blood serum and prepared sequencing libraries from a low amount of RNA. High-throughput sequencing identified differential levels of 460 transcripts between CRC patients and healthy controls, including mRNAs, lncRNAs, and pseudogenes, with approximately 20% being lncRNAs, highlighting several tumor-specific lncRNAs that have not been associated with CRC development and progression. The validation phase confirmed the upregulation of three lncRNAs (NALT1, AL096828, and LINC01637) in blood serum of CRC patients. This study not only identified lncRNA profiles in a population of sEVs from low-volume blood serum specimens of CRC patients but also highlights the value of innovative techniques in biomolecular research, particularly for the detection and analysis of low-abundance biomolecules in clinical samples. The identification of specific lncRNAs associated with CRC provides a foundation for future research into their functional roles in cancer development and potential clinical applications.
- Klíčová slova
- Biomarker, Colorectal cancer, EVs, lncRNAs,
- MeSH
- biologické markery MeSH
- extracelulární vezikuly * genetika MeSH
- kolorektální nádory * diagnóza genetika MeSH
- lidé MeSH
- RNA dlouhá nekódující * genetika MeSH
- sekundární malignity * MeSH
- sérum MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- RNA dlouhá nekódující * MeSH
Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of various tumors through multiple mechanisms. Among these, HOTTIP (HOXA transcript at the distal tip) stands out as an intriguing candidate with diverse functions in several malignancies, including breast cancer and gynecologic cancers such as ovarian, cervical, and endometrial cancers, which are significant global health concerns. HOTTIP interacts with key signaling pathways associated with these cancers, including Wnt/β-catenin, PI3K/AKT, and MEK/ERK pathways, enhancing their activation and downstream effects. Its influence extends to crucial aspects of cancer biology, such as cell proliferation, apoptosis, migration, invasion, angiogenesis, and epithelial-mesenchymal transition (EMT). Additionally, HOTTIP plays a pivotal role in the pathogenesis of breast and gynecologic tumors by sponging various microRNAs (miRNAs) and regulating the expression of mRNAs involved in critical molecular processes. This dysregulation is often associated with poor clinical outcomes, advanced disease stages, and distant metastases. Understanding the functional roles of HOTTIP in these cancers is essential for developing targeted therapeutic strategies. This review aims to explore the emerging roles of HOTTIP in breast and gynecologic cancers.
- Klíčová slova
- Gynecologic cancers, HOTTIP, lncRNAs, targeted therapy.,
- Publikační typ
- časopisecké články MeSH