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.

• 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

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.

• 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 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.

• 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

Východiska: Invazivní duktální karcinom (invasive ductal carcinoma – IDC) je nejčastějším typem karcinomu prsu (breast cancer – BC) u žen s vysokou klinickou zátěží v důsledku svých vysoce invazivních vlastností. I přes to, že se rychle objevují nová data týkající se molekulární heterogenity invazivních karcinomů, mnohem méně je známo o molekulárních vzorcích IDC. Stále se zvyšující množství důkazů ukázalo, že heterogenní povaha BC souvisí s dysregulací dlouhých nekódujících RNA (long noncoding RNAs – lncRNAs). Metody: V této studii jsme analyzovali hladinu exprese dvou nových lncRNAs, LOC100288637 a RP11-48B3, v 51 tkáních IDC, které jsme porovnali s přilehlými nekancerózními tkáněmi. Nakonec bylo provedeno bioinformatické hodnocení. Výsledky: Výsledky kvantitativní polymerázové řetězové reakce ukázaly, že LOC100288637 a RP11-48B3 byly v nádorové tkáni významně overexprimovány, a to v porovnání s normálními vzorky (p = 0,0085 a p = 0,0002). Tyto dvě lncRNAs byly také overexprimovány jak v buněčné linii MDA-MB-231 tak v MCF-7 BC, ovšem v buněčné linii MDA-MB-231 byl pozorován vyšší vzorec exprese než u MCF7. Navíc LOC100288637 měl zvýšenou hladinu exprese u HER-2 pozitivních nádorů v porovnání s HER-2 negativními nádory (p = 0,031). Je zajímavé, že lncRNA RP11-48B3.4 byla upregulována u subjektů s IDC a menarche ve věku < 14 let, a to v porovnání s pacientkami s menarche ve věku ≥ 14 let (p = 0,041). Při jiném výsledku bylo pozorováno, že lncRNA RP11-48B3.4 je významně upregulována u nádorů nižšího histologického grade v porovnání se vzorky nádorů s vyšším grade (p = 0,047). A nakonec jsme pomocí bioinformatického hodnocení našli předpokládanou interakci mezi RP11-48B3.4 a mRNA „zinc finger and BTB domain containing 10“. Závěr: Naše zjištění svědčí o tom, že tyto lncRNAs, které potenciálně hrají onkogenní roli, jsou klinicky významně zapojeny do patogeneze IDC a mohou tedy sloužit jako nové markery pro diagnostiku a léčbu IDC.

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, bioinformatic 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 bioinformatic 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 diagnosis and treatment of IDC.

• Klíčová slova
• LOC100288637, RP11-48B3,
• MeSH
• duktální karcinom prsu * genetika   patofyziologie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• nekódující RNA MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví 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.

• Publikační typ
• časopisecké články MeSH
• přehledy 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.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Breast cancer is a prevalent and aggressive disease characterized by high metastasis, recurrence, and mortality rates. While cisplatin is an effective chemotherapy drug, its use is limited by its toxic effects on the body. Despite advancements in therapeutic strategies, the therapeutic response is often unsatisfactory due to drug resistance, leading to poor prognosis. Recent studies have shown that cisplatin interacts with long non-coding RNAs (lncRNAs) and accelerates the development of resistance in tumor cells to therapy. This interaction highlights the complex mechanisms involved in the response of cancer cells to chemotherapy. Several lncRNAs have been identified as key players in mediating cisplatin resistance in breast cancer. These lncRNAs include SNHG15, HULC, HCP5, MT1JP, LncMat2B, DLX6-ASL, Linc00665, CARMN, and Lnc-EinRP44-3:6. These lncRNAs have been shown to target microRNAs and mRNAs and modulate the expression of genes involved in cisplatin resistance, which is important in treating breast cancer.

• MeSH
• antitumorózní látky * terapeutické užití   farmakologie   MeSH
• chemorezistence * genetika   MeSH
• cisplatina * terapeutické užití   farmakologie   MeSH
• lidé MeSH
• nádory prsu * farmakoterapie   genetika   patologie   metabolismus   MeSH
• regulace genové exprese u nádorů * účinky léků   MeSH
• RNA dlouhá nekódující * genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Long non-coding RNAs (lncRNAs) are defined as RNA molecules longer than 200 nucleotides with poor protein-coding capacity and key functions in regulation of gene expression. Dysregulations of lncRNAs (e.g. HOTAIR and MALAT I) were detected in plasma of breast cancer (BC) patients. Plasma samples are examined as liquid biopsies for purposes of non-invasive diagnostics therefore the research of plasma lncRNAs as potential plasma biomarkers became highly topical. 84 lncRNAs were profiled in 18 plasma samples - 9 BC patients and 9 age-matched healthy - using Human Inflammatory Response & Autoimmunity RT2 lncRNA PCR Array. Total RNA from plasma samples was isolated using miRNeasy Serum/Plasma Kit. Although a pre-amplification recommended for quantification from small starting RNA amounts was used, only 3 lncRNAs (A2ML1-AS1, GAS5 and SNHG5) were detected in all plasma samples. A total of 72 lncRNAs (e.g. HOTAIR or MALAT I) were detected only in some samples and 9 lncRNAs were not detected in any samples. No significant differences were observed in levels of plasma lncRNAs between the BC patients and healthy controls despite the fact that our panel contained also the lncRNAs whose levels were previously reported as significantly different in plasma or cancer tissues (e.g. GAS5, HOTAIR, MALAT I) in BC patients. Detection of lncRNAs in plasma is due to their low concentrations quite difficult as compared with tissues. Our findings suggest that analysis of plasma lncRNAs using this technology is not suitable for use as non-invasive diagnostic tool in BC patients.

• MeSH
• lidé MeSH
• nádory prsu diagnóza   genetika   MeSH
• polymerázová řetězová reakce * MeSH
• regulace genové exprese u nádorů MeSH
• RNA dlouhá nekódující krev   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH