Die Rolle von miRNA bei Kopf-Hals-Malignomen

 

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Zusammenfassung

In den vergangenen Jahren hat sich das Langzeitüberleben beim Plattenepithelkarzinom im Kopf-Halsbereich (KH-PECA) trotz optimierter Therapiemaßnahmen nur geringfügig verbessert. Die meisten Studien zum Genom der Tumorzellen fokussieren auf Protein-kodierende Gene (Exons). Daten über Veränderungen der nicht-kodierenden Sequenzen (Introns) sind begrenzt. miRNAs (microRNA, miR) sind kleine, nicht-kodierende einzelsträngige RNAs, die die Genexpression auf posttranskriptionaler Ebene durch Interaktion mit der mRNA kontrollieren. miRNA-Funktionen umfassen zahlreiche biologische Prozesse und regulieren nach Hochrechnungen bis zu 50% der menschlichen Gene. Sie können onkogen oder tumorsuppressiv sein. Veränderte Expressionsmuster der miRNA sind mit der Karzinogenese und Tumorprogression auch bei den KH-PECA bzw. denjenigen Prozessen beteiligt (erhöhte Resistenz gegenüber Strahlen- oder Chemotherapie), die für die anhaltend schlechte Prognose durch Bildung von Metastasen und inoperablen Rezidiven verantwortlich sein könnten. Daher werden hier die miRNA Gruppen vorgestellt, die eine Bedeutung für diese Prozesse besitzen und die somit auch als mögliche Zielstrukturen neuer Therapien dienen könnten. miRNA können möglicherweise zudem als Biomarker für die frühe Diagnose, Prognose, Bewertung der Behandlung und Überwachung eines Rezidivs dienen. Eine Veränderung der miRNA-Expression in KH-PECA vor und nach Chemotherapie ist daher von großem Interesse. Langfristig könnten diese Erkenntnisse zu wirksameren Therapien führen, die die Prognose von KH-PECA verbessern.

Abstract

Despite optimized therapeutic strategies, the long-term survival of head and neck squamous cell carcinomas (HNSCC) has improved in recent years only slightly. Most studies on the tumor cell genome focus on protein-coding genes (exons). Data on changes within the non-coding sequences (introns) are limited. miRNAs (microRNA, miR) are small non-coding single-stranded RNAs that control gene expression at the posttranscriptional level by interacting with the mRNA. miRNA functions include many biological processes and control up to 50 % of human genes. They can have oncogenic or tumor suppressive functions. Altered expression patterns of miRNAs are involved in carcinogenesis and tumor progression even in HNSCC, or those processes (increased resistance to radiation or chemotherapy) that could be responsible for the poor long-term prognosis by forming metastases and inoperable local recurrences. Therefore, we here present miRNA groups, which are involved in these processes and may serve as new potential therapeutic treatment targets. miRNAs may also serve as biomarkers for early diagnosis, evaluation and monitoring of treatment and tumor recurrence. Alterations in miRNA expression before and after chemotherapy are therefore of high interest. In the long run, this knowledge could lead to more effective therapies with improved therapeutic outcome of HNSCC.

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