微小RNA在KRAS和NRAS突变型结直肠癌中的表达

MicroRNA Expression in - and -mutated Colorectal Cancers.

作者信息

Lundberg Ida V, Wikberg Maria L, Ljuslinder Ingrid, Li Xingru, Myte Robin, Zingmark Carl, Löfgren-Burström Anna, Edin Sofia, Palmqvist Richard

机构信息

Department of Medical Biosciences, Pathology, Umeå University, Umea, Sweden

Department of Medical Biosciences, Pathology, Umeå University, Umea, Sweden.

出版信息

Anticancer Res. 2018 Feb;38(2):677-683. doi: 10.21873/anticanres.12272.

DOI:10.21873/anticanres.12272

PMID:29374690

Abstract

BACKGROUND/AIM: KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS- and BRAF-mutated CRCs.

MATERIALS AND METHODS

Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF.

RESULTS

Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors.

CONCLUSION

Our results suggest that KRAS- and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS- and BRAF-mutated tumors was evident for the miRNAs analyzed in this study.

摘要

背景/目的：KRAS和BRAF是在结直肠癌（CRC）中常见的两个突变基因。尽管BRAF是丝裂原活化蛋白激酶（MAPK）信号通路中KRAS的下游靶点，但发现KRAS和BRAF突变的结直肠癌表现出几种不同的临床和组织病理学特征。我们研究了微小RNA（miRNA）的差异表达是否可以解释KRAS和BRAF突变的结直肠癌之间的临床病理差异。

材料与方法

使用PCR阵列，我们分析了KRAS和BRAF野生型、KRAS或BRAF突变的结直肠癌细胞系中84种不同miRNA的表达。

结果

选择了10种miRNA在肿瘤组织标本中进行进一步分析（let-7a、let-7i、miR-10a、miR-10b、miR-31、miR-100、miR-181a、miR-181b、miR-372和miR-373）。与野生型肿瘤相比，发现BRAF突变的肿瘤中miR-31表达水平显著更高，而miR-373水平显著更低。