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.

结直肠癌 (CRC) 是基因突变积累和信号通路改变的结果。KRAS在 40% 的 CRC 病例中发生突变，并参与增加肿瘤细胞的增殖和存活。尽管KRAS突变是 CRC 肿瘤发生的主要事件，但野生型 KRAS 表达的增加对加速肿瘤生长也有类似的影响。在这项研究中，我们研究了 KRAS 状态与散发性 CRC 的临床病理特征的相关性，更重要的是let-7a-5p和miR-544a-3p在调节肿瘤中心（T1 ) 和浸润性肿瘤前沿 (T2)。分析表明，39.1% 的肿瘤样本具有KRAS突变。在野生型KRAS肿瘤中，62.0% 的 KRAS 蛋白表达呈阳性，T2 中 KRAS 阳性肿瘤细胞的百分比和免疫组织化学反应强度高于 T1 样本。这不能归因于KRAS mRNA 水平的差异，表明通过miR-544a-3p表达的调节在 T2 样品中显着降低。此外，我们证明携带KRAS-LCS6变异等位基因的肿瘤样本具有显着更高的野生型 KRAS 蛋白质表达。我们的结果表明KRAS-LCS6多态性和miR-544a-3p 的作用 表达在散发性 CRC 中野生型 KRAS 蛋白表达的调节中。