Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma

• DOI: 10.1007/s13577-021-00576-2
• Publication Date: 2021-07-07T18:13:02Z
• Authors: Sonja Marinović; Anita Škrtić; Tina Catela Ivković; Mirko Poljak; Sanja Kapitanović
• Keywords: Colon adenocarcinoma ; Immunohistochemistry ; KRAS ; let-7a ; miR-544a; Adult; Aged, 80 and over; Male; 0301 basic medicine; Gene Expression; Human Genetics, Genomics and Proteomics; Adenocarcinoma; Middle Aged; Polymorphism, Single Nucleotide; Gene Expression Regulation, Neoplastic; Proto-Oncogene Proteins p21(ras); MicroRNAs; 03 medical and health sciences; Colonic Neoplasms; Humans; Female; Aged

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.