BACKGROUND/AIM: MicroRNAs (miRs) play an important role in the regulation of cancer-related processes and are promising candidates for cancer biomarkers. The aim of the study was to evaluate the association of response to anti-EGFR monoclonal antibodies (mAbs) with selected miR expression profiles, including miR-125b, let-7c, miR-99a, miR-17, miR-143 and miR-145 in metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: This retrospective study included 46 patients with mCRC harbouring wild-type RAS gene treated with cetuximab or panitumumab combined with chemotherapy in first- or second-line therapy. The miR expression was assessed using qRT-PCR. RESULTS: Down-regulation of miR-125b and let-7c and up-regulation of miR-17 were found in the tumour tissue (p=0.0226, p=0.0040, p<0.0001). Objective response rate (ORR) was associated with up-regulation of miR-125b (p=0.0005). Disease control rate (DCR) was associated with up-regulation of miR-125b and let-7c (p=0.0383 and p=0.0255) and down-regulation of miR-17 (p=0.0464). MiR-125b showed correlation with progression-free and overall survival (p=0.055 and p=0.006). CONCLUSION: The results show that up-regulation of miR-125b is associated with higher ORR and DCR and longer survival; let-7c up-regulation and miR-17 down-regulation are associated with higher DCR in mCRC patients treated with anti-EGFR mAbs.

• Klíčová slova
• Colorectal cancer, cetuximab, chemotherapy, let-7c, miR-125b, miR-17, microRNA, panitumumab,
• MeSH
• cetuximab farmakologie   terapeutické užití   MeSH
• chemorezistence genetika   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• down regulace MeSH
• erbB receptory antagonisté a inhibitory   genetika   MeSH
• inhibitory proteinkinas farmakologie   terapeutické užití   MeSH
• kolorektální nádory farmakoterapie   genetika   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• panitumumab farmakologie   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cetuximab MeSH
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• inhibitory proteinkinas MeSH
• mikro RNA MeSH
• MIRN125 microRNA, human MeSH Prohlížeč
• MIRN17 microRNA, human MeSH Prohlížeč
• mirnlet7 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• panitumumab MeSH

MicroRNAs (miRNAs) constitute a robust regulatory network with post-transcriptional regulatory efficiency for almost one half of human coding genes, including oncogenes and tumour suppressors. We determined the expression profile of 667 miRNAs in colorectal cancer (CRC) tissues and paired non-tumoural tissues and identified 42 differentially expressed miRNAs. We chose miR-215, miR-375, miR-378, miR-422a and miR-135b for further validation on an independent cohort of 125 clinically characterized CRC patients and for in vitro analyses. MiR-215, miR-375, miR-378 and miR-422a were significantly decreased, whereas miR-135b was increased in CRC tumour tissues. Levels of miR-215 and miR-422a correlated with clinical stage. MiR-135b was associated with higher pre-operative serum levels of CEA and CA19-9. In vitro analyses showed that ectopic expression of miR-215 decreases viability and migration, increases apoptosis and promotes cell cycle arrest in DLD-1 and HCT-116 colon cancer cell lines. Similarly, overexpression of miR-375 and inhibition of miR-135b led to decreased viability. Finally, restoration of miR-378, miR-422a and miR-375 inhibited G1/S transition. These findings indicate that miR-378, miR-375, miR-422a and miR-215 play an important role in CRC as tumour suppressors, whereas miR-135b functions as an oncogene; both groups of miRNA contribute to CRC pathogenesis.

• MeSH
• apoptóza genetika   MeSH
• dospělí MeSH
• kolorektální nádory genetika   patologie   MeSH
• kontrolní body buněčného cyklu genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• nádorové buněčné linie MeSH
• pohyb buněk genetika   MeSH
• regulace genové exprese u nádorů * MeSH
• reprodukovatelnost výsledků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tumor supresorové geny MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN135 microRNA, human MeSH Prohlížeč
• MIRN215 microRNA, human MeSH Prohlížeč
• MIRN375 microRNA, human MeSH Prohlížeč
• MIRN378 microRNA, human MeSH Prohlížeč
• MIRN422 microRNA, human MeSH Prohlížeč

The KRAS gene (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is an oncogene that encodes a small GTPase transductor protein called KRAS. KRAS is involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus. Activating mutations in the KRAS gene impair the ability of the KRAS protein to switch between active and inactive states, leading to cell transformation and increased resistance to chemotherapy and biological therapies targeting epidermal growth factor receptors. This review highlights some of the features of the KRAS gene and the KRAS protein and summarizes current knowledge of the mechanism of KRAS gene regulation. It also underlines the importance of activating mutations in the KRAS gene in relation to carcinogenesis and their importance as diagnostic biomarkers, providing clues regarding human cancer patients' prognosis and indicating potential therapeutic approaches.

• MeSH
• lidé MeSH
• nádory * genetika   metabolismus   terapie   MeSH
• protoonkogenní proteiny p21(ras) MeSH
• protoonkogenní proteiny * MeSH
• Ras proteiny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• KRAS protein, human MeSH Prohlížeč
• protoonkogenní proteiny p21(ras) MeSH
• protoonkogenní proteiny * MeSH
• Ras proteiny * MeSH

MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Changes in the expression profiles of miRNAs have been observed in a variety of human tumors, including colorectal cancer (CRC). Functional studies indicate that miRNAs act as tumor suppressors and oncogenes. These findings significantly extend Vogelstein's model of CRC pathogenesis and have shown great potential for miRNAs as a novel class of therapeutic targets. Several investigations have also described the ability of miRNA expression profiles to predict prognosis and response to selected treatments in CRC patients, and support diagnosis of CRC among cancer of unknown primary site. miRNAs' occurrence has been repeatedly observed also in serum and plasma, and miRNAs as novel minimally invasive biomarkers have indicated reasonable sensitivity for CRC detection and compare favorably with the fecal occult blood test. In this review, we summarize the knowledge regarding miRNAs' functioning in CRC while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets.

• MeSH
• kolorektální nádory krev   diagnóza   etiologie   genetika   MeSH
• lidé MeSH
• mikro RNA krev   genetika   metabolismus   MeSH
• molekulární biologie * MeSH
• polymorfismus genetický MeSH
• stanovení celkové genové exprese MeSH
• translační biomedicínský výzkum * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH