Long non-coding RNAs (lncRNAs) are DNA transcripts longer than 200 nucleotides without protein-coding potential. As they are key regulators of gene expression at chromatic, transcriptional and posttranscriptional level, they play important role in various biological and pathological processes. Dysregulation of lncRNAs has been observed in several diseases including cancer. Breast cancer is heterogeneous disease with many molecular subtypes specific in different prognosis and treatment responses. Hypoxia, a common micro-environmental feature of rapidly growing tumour is associated with metastases, recurrences and resistance to therapy. Aberrant expression of hypoxia related lncRNAs significantly correlates with poor outcomes in cancer patients, as the lncRNAs play an important regulatory role in the breast cancer-cell survival. Thus, a better understanding of lncRNAs role in the hypoxic conditions of breast cancer is crucial for precise understanding of the tumorigenesis, disease features and poor clinical outcome, especially in highly aggressive breast cancer subtypes (HER2-positive and triple-negative types). Moreover, lncRNAs may represent tumour marker predicting prognosis and therapeutic targets improving precise and personalized therapy for better patient´s survival. In this review, we summarize the recent information on lncRNAs in breast cancer with special focus on the hypoxia-responsive lncRNAs and their potential impact on the prognosis, therapy algorithms and individual outcomes. Presented data helps in better understanding of the specific mechanisms predicting new therapeutic agents and strategies for the pharmacological intervention.
- MeSH
- Cell Hypoxia genetics MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Breast Neoplasms genetics pathology therapy MeSH
- RNA, Long Noncoding genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Bielkoviny tepelného šoku (heat shock proteins – HSPs) HSP27, HSP70 a HSP90 sú molekulárne šaperóny, ktorých expresia sa zvyšuje ovplyvnením buniek po pôsobení enviromentálneho stresu, akými sú tepelný šok, ťažké kovy, oxidačný stres alebo pri patologických podmienkach ako napr. ischémia, infekcia a zápal. Ich protektívna úloha pomáha bunke vyrovnať sa s letálnymi podmienkami. HSPs sú skupina bielkovín, ktoré v zdravých bunkách zodpovedajú za udržanie homeostázy, za interakciu s rôznymi bielkovinovými substrátmi na zabezpečenie ich správneho zbalenia, zabraňujú zbaľovaniu intermediátorov, ktoré vedú ku tvorbe chybne zbalených alebo poškodených molekúl. Ukázalo sa, že interagujú s rôznymi kľúčovými bielkovinami a zohrávajú úlohu v regulácii apoptózy. Viaceré bielkoviny tepelného šoku preukázali priamu interakciu s rozličnými zložkami úzko regulovanej kaspázovo-závislej programovanej bunkovej smrti. Tieto bielkoviny rovnako ovplyvňujú kaspázovo-nezávislú dráhu apoptózy väzbou s apoptickými faktormi. Bielkoviny tepelného šoku sú odlišne exprimované v hematologických malignitách. Z dôvodu ich asociácie a úlohy v leukémiách, HSPs predstavujú zaujímavý cieľ v antileukemickej terapii. Tento prehľadový článok opisuje rôzne molekuly intaragujúce s antiapoptotickými bielkovinami HSP70 a HSP90, ktoré by mohli byť využité v nádorovej terapii na základe ich inhibície. Klúčové slová:bielkoviny tepelného šoku – inhibítory – leukémia – apoptóza Táto práca bola podporená grantom „Zvýšenie možností kariérneho rastu vo výskume a vývoji v oblasti lekárskych vied“ (IMTS 26110230067), operačný program Vzdelávanie, doc. MUDr. Ján Staško, PhD., mim. prof., 2012–2015. Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy. Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů. Obdržané: 7. 8. 2015 Prijaté: 11. 10. 2015
Heat shock proteins (HSPs) HSP27, HSP70 and HSP90 are molecular chaperones; their expression is increased after exposure of cells to conditions of environmental stress, including heat shock, heavy metals, oxidative stress, or pathologic conditions, such as ischemia, infection, and inflammation. Their protective function is to help the cell cope with lethal conditions. The HSPs are a class of proteins which, in normal cells, are responsible for maintaining homeostasis, interacting with diverse protein substrates to assist in their folding, and preventing the appearance of folding intermediates that lead to misfolded or damaged molecules. They have been shown to interact with different key apoptotic proteins and play a crucial role in regulating apoptosis. Several HSPs have been demonstrated to directly interact with various components of tightly regulated caspase-dependent programmed cell death. These proteins also affect caspase-independent apoptosis by interacting with apoptogenic factors. Heat shock proteins are aberrantly expressed in hematological malignancies. Because of their prognostic implications and functional role in leukemias, HSPs represent an interesting target for antileukemic therapy. This review will describe different molecules interacting with anti-apoptotic proteins HSP70 and HSP90, which can be used in cancer therapy based on their inhibition.
- MeSH
- Apoptosis physiology MeSH
- Clinical Trials as Topic MeSH
- Clinical Trials, Phase I as Topic MeSH
- Clinical Trials, Phase II as Topic MeSH
- Leukemia drug therapy MeSH
- Humans MeSH
- HSP27 Heat-Shock Proteins physiology metabolism MeSH
- HSP70 Heat-Shock Proteins antagonists & inhibitors physiology metabolism drug effects MeSH
- HSP90 Heat-Shock Proteins antagonists & inhibitors physiology metabolism drug effects MeSH
- Heat-Shock Proteins * physiology metabolism drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
