Colorectal carcinoma (CRC) results from the accumulation of genetic mutations and alterations in signaling pathways. KRAS is mutated in 40% of CRC cases and is involved in increased tumor cells proliferation and survival. Although KRAS mutations are a dominant event in CRC tumorigenesis, increased wild-type KRAS expression has a similar effect on accelerated tumor growth. In this study, we investigated the KRAS status in correlation with clinicopathological features in sporadic CRC and more importantly the role of let-7a-5p and miR-544a-3p in the regulation of wild-type KRAS protein expression in the tumor center (T1) and invasive tumor front (T2). Analysis showed that 39.1% of tumor samples had KRAS mutations. In wild-type KRAS tumors, 62.0% were positive for KRAS protein expression and there was a higher percentage of KRAS-positive tumor cells and a higher intensity of immunohistochemical reaction in T2 than in T1 samples. This could not be attributed to differences in KRAS mRNA levels, suggesting regulation via miR-544a-3p expression which was significantly decreased in T2 samples. Furthermore, we demonstrated that tumor samples carrying the KRAS-LCS6 variant allele had significantly higher protein expression of the wild-type KRAS. Our results suggest the role of the KRAS-LCS6 polymorphism and miR-544a-3p expression in the regulation of wild-type KRAS protein expression in sporadic CRC.

• Klíčová slova
• Colon adenocarcinoma, Immunohistochemistry, KRAS, Let-7a, miR-544a,
• MeSH
• adenokarcinom genetika   patologie   MeSH
• dospělí MeSH
• exprese genu genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   fyziologie   MeSH
• nádory tračníku genetika   patologie   MeSH
• protoonkogenní proteiny p21(ras) genetika   metabolismus   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• senioři nad 80 let MeSH
• senioři 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
• KRAS protein, human MeSH Prohlížeč
• mikro RNA MeSH
• MIRN544 microRNA, human MeSH Prohlížeč
• protoonkogenní proteiny p21(ras) MeSH