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

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

LncRNA PVT1 (plasmacytoma variant translocation 1) has become a staple of the lncRNA profile in patients with renal cell carcinoma (RCC). Common dysregulation in renal tumors outlines the essential role of PVT1 in the development of RCC. There is already a plethora of publications trying to uncover the cellular mechanisms of PVT1-mediated regulation and its potential exploitation in management of RCC. In this review, we summarize the literature focused on PVT1 in RCC and aim to synthesize the current knowledge on its role in the cells of the kidney. Further, we provide an overview of the lncRNA profiling studies that have identified a more or less significant association of PVT1 with the clinical behavior of RCC. Based on our search, we analyzed the 17 scientific papers discussed in this review that provide robust support for the indispensable role of PVT1 in RCC development and future personalized therapy.

• MeSH
• karcinom z renálních buněk genetika   MeSH
• lidé MeSH
• nádory ledvin genetika   MeSH
• pohyb buněk MeSH
• prognóza MeSH
• proliferace buněk MeSH
• regulace genové exprese u nádorů MeSH
• RNA dlouhá nekódující genetika   MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Tens of thousands of rapidly evolving long non-coding RNA (lncRNA) genes have been identified, but functions were assigned to relatively few of them. The lncRNA contribution to the mouse oocyte physiology remains unknown. We report the evolutionary history and functional analysis of Sirena1, the most expressed lncRNA and the 10th most abundant poly(A) transcript in mouse oocytes. Sirena1 appeared in the common ancestor of mouse and rat and became engaged in two different post-transcriptional regulations. First, antisense oriented Elob pseudogene insertion into Sirena1 exon 1 is a source of small RNAs targeting Elob mRNA via RNA interference. Second, Sirena1 evolved functional cytoplasmic polyadenylation elements, an unexpected feature borrowed from translation control of specific maternal mRNAs. Sirena1 knock-out does not affect fertility, but causes minor dysregulation of the maternal transcriptome. This includes increased levels of Elob and mitochondrial mRNAs. Mitochondria in Sirena1-/- oocytes disperse from the perinuclear compartment, but do not change in number or ultrastructure. Taken together, Sirena1 contributes to RNA interference and mitochondrial aggregation in mouse oocytes. Sirena1 exemplifies how lncRNAs stochastically engage or even repurpose molecular mechanisms during evolution. Simultaneously, Sirena1 expression levels and unique functional features contrast with the lack of functional importance assessed under laboratory conditions.

• MeSH
• genový knockout MeSH
• krysa rodu rattus MeSH
• messenger RNA genetika   MeSH
• mitochondrie genetika   ultrastruktura   MeSH
• myši MeSH
• oocyty růst a vývoj   metabolismus   ultrastruktura   MeSH
• polyadenylace genetika   MeSH
• RNA dlouhá nekódující genetika   MeSH
• RNA mitochondriální genetika   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chromatin architect of muscle expression (Charme) is a muscle-restricted long noncoding RNA (lncRNA) that plays an important role in myogenesis. Earlier evidence indicates that the nuclear Charme isoform, named pCharme, acts on the chromatin by assisting the formation of chromatin domains where myogenic transcription occurs. By combining RNA antisense purification (RAP) with mass spectrometry and loss-of-function analyses, we have now identified the proteins that assist these chromatin activities. These proteins-which include a sub-set of splicing regulators, principally PTBP1 and the multifunctional RNA/DNA binding protein MATR3-bind to sequences located within the alternatively spliced intron-1 to form nuclear aggregates. Consistent with the functional importance of pCharme interactome in vivo, a targeted deletion of the intron-1 by a CRISPR-Cas9 approach in mouse causes the release of pCharme from the chromatin and results in cardiac defects similar to what was observed upon knockout of the full-length transcript.

• MeSH
• heterogenní jaderné ribonukleoproteiny metabolismus   MeSH
• introny genetika   MeSH
• lidé MeSH
• myši MeSH
• protein vázající polypyrimidinové úseky RNA metabolismus   MeSH
• proteiny asociované s jadernou matrix metabolismus   MeSH
• proteiny vázající RNA metabolismus   MeSH
• RNA dlouhá nekódující metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The plant genome can produce long non-coding RNAs (lncRNAs), some of which have been identified as important regulators of gene expression. To better understand the response mechanism of rice plants to Rice black-streaked dwarf virus (RBSDV) infection, we performed a comparative transcriptome analysis between the RBSDV-infected and non-infected rice plants. A total of 1342 mRNAs and 22 lncRNAs were identified to be differentially expressed after RBSDV infection. Most differentially expressed transcripts involved in the plant-pathogen interaction pathway were upregulated after RBSDV infection, indicating the activation of rice defense response by RBSDV. A network of differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) was then constructed. In this network, there are 56 plant-pathogen interaction-related DEmRNAs co-expressing with 20 DElncRNAs, suggesting these DElncRNAs and DEmRNAs may play essential roles in rice innate immunity against RBSDV. Moreover, some of the lncRNA-mRNA regulatory relationships were experimentally verified in rice calli by a quick and effective method established in this study. Three DElncRNAs were selected to be tested, and the results indicated that five mRNAs were found to be regulated by them. Together, we give a whole landscape of rice mRNAs and lncRNAs in response to RBSDV infection, and a feasible method to rapidly verify the lncRNA-mRNA regulatory relationship in rice.

• MeSH
• messenger RNA genetika   metabolismus   MeSH
• nemoci rostlin genetika   virologie   MeSH
• regulace genové exprese u rostlin * MeSH
• RNA dlouhá nekódující genetika   metabolismus   MeSH
• RNA rostlin genetika   metabolismus   MeSH
• rostlinné viry genetika   fyziologie   MeSH
• stanovení celkové genové exprese MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

BACKGROUND: Renal cell carcinoma is difficult to diagnose and unpredictable in disease course and severity. There are no specific biomarkers for diagnosis and prognosis estimation feasible in clinical practice. Long non-coding RNAs (lncRNAs) have emerged as potent regulators of gene expression in recent years. Aside from their cellular role, their expression patterns could be used as a biomarker of ongoing pathology. METHODS: In this work, we used next-generation sequencing for global lncRNA expression profiling in tumor and non-tumor tissue of RCC patients. The four candidate lncRNAs have been further validated on an independent cohort. PVT1, as the most promising lncRNA, has also been studied using functional in vitro tests. RESULTS: Next-generation sequencing showed significant dysregulation of 1163 lncRNAs; among them top 20 dysregulated lncRNAs were AC061975.7, AC124017.1, AP000696.1, AC148477.4, LINC02437, GATA3-AS, LINC01762, LINC01230, LINC01271, LINC01187, LINC00472, AC007849.1, LINC00982, LINC01543, AL031710.1, and AC019197.1 as down-regulated lncRNAs; and SLC16A1-AS1, PVT1, LINC0887, and LUCAT1 as up-regulated lncRNAs. We observed statistically significant dysregulation of PVT1, LUCAT1, and LINC00982. Moreover, we studied the effect of artificial PVT1 decrease in renal cell line 786-0 and observed an effect on cell viability and migration. CONCLUSION: Our results show not only the diagnostic but also the therapeutic potential of PVT1 in renal cell carcinoma.

• MeSH
• karcinom z renálních buněk * genetika   patofyziologie   MeSH
• lidé MeSH
• nádorové biomarkery genetika   fyziologie   MeSH
• nádorové buněčné linie MeSH
• nádory ledvin * genetika   patofyziologie   MeSH
• pohyb buněk genetika   MeSH
• proliferace buněk genetika   MeSH
• regulace genové exprese u nádorů MeSH
• RNA dlouhá nekódující * genetika   metabolismus   fyziologie   MeSH
• viabilita buněk genetika   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články 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

• MeSH
• dítě MeSH
• kojenec MeSH
• leukemie genetika   metabolismus   patologie   MeSH
• lidé MeSH
• mladiství MeSH
• nádorové proteiny biosyntéza   genetika   MeSH
• předškolní dítě MeSH
• proteiny vázající RNA biosyntéza   genetika   MeSH
• regulace genové exprese u leukemie * MeSH
• RNA dlouhá nekódující genetika   metabolismus   MeSH
• RNA nádorová genetika   metabolismus   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH