Swiercz Aneta, Chechlinska Magdalena, Kupryjanczyk Jolanta, Dansonka-Mieszkowska Agnieszka, Rembiszewska Alina, Goryca Krzysztof, Kulinczak Mariusz, Zajdel Michalina, Sromek Maria, Siwicki Jan Konrad
Department of Immunology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.
Department of Immunology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
Anticancer Res. 2015 Apr;35(4):2423-9.
BACKGROUND/AIM: miR-7 has recently been linked to cancer. Some miR-7 targets, including B-cell lymphoma 2 (BCL2) and epidermal growth factor receptor (EGFR), are involved in ovarian cancer (OC) pathogenesis. The majority of OCs display TP53 mutations, which are critically important for OC development. We aimed to study the expression level of miR-7 and of two of its postulated target genes, BCL2 and EGFR, in serous ovarian carcinomas of different TP53 status and tumour grade.
Gene and miR expression was assessed by real-time reverse transcription polymerase chain reaction in 45 clinical samples of low- (G1+G2) and high- (G3) grade primary serous OC with wild-type (wt) or mutated TP53, as well as in three OC cell lines, each representing a different TP53 status. The results obtained in patients with OC were analysed against their disease-free survival (DFS).
In high-grade OC with TP53 mutations, the level of miR-7 expression significantly exceeded (by several fold) that in wtTP53 cancer (p<0.01). Within the wtTP53 tumour series, the level of miR-7 expression was significantly higher (by over 10-fold) in high-grade than in low-grade OC (p<0.01). miR-7 expression was not found to influence DFS. The differences in miR-7 expression depending on TP53 status found in clinical OC samples were not observed in OC cell lines. miR-7 overexpression correlated with diminished BCL2 expression, but there was no relationship between miR-7 and EGFR expression, neither in tumour samples nor in the cell lines.
There is a link between miR-7 expression and TP53 status and tumour grade in serous OC. Molecular mechanisms of these relationships need to be elucidated. Of the two postulated miR-7 target genes we examined, BCL2, but not EGFR, seems to be a possible miR-7 target in OC.
背景/目的:miR-7最近被认为与癌症有关。一些miR-7的靶标,包括B细胞淋巴瘤2(BCL2)和表皮生长因子受体(EGFR),参与了卵巢癌(OC)的发病机制。大多数OC显示TP53突变,这对OC的发展至关重要。我们旨在研究miR-7及其两个假定靶基因BCL2和EGFR在不同TP53状态和肿瘤分级的浆液性卵巢癌中的表达水平。
通过实时逆转录聚合酶链反应评估45例低级别(G1+G2)和高级别(G3)原发性浆液性OC临床样本中基因和miR的表达,这些样本具有野生型(wt)或突变型TP53,同时评估三种OC细胞系中的表达,每个细胞系代表不同的TP53状态。将OC患者获得的结果与其无病生存期(DFS)进行分析。
在具有TP53突变的高级别OC中,miR-7表达水平显著超过(几倍)wtTP53癌症中的水平(p<0.01)。在wtTP53肿瘤系列中,高级别OC中miR-7表达水平显著高于低级别OC(超过10倍)(p<0.01)。未发现miR-7表达影响DFS。在OC细胞系中未观察到临床OC样本中根据TP53状态发现的miR-7表达差异。miR-7过表达与BCL2表达降低相关,但在肿瘤样本和细胞系中,miR-7与EGFR表达之间均无关联。
浆液性OC中miR-7表达与TP53状态和肿瘤分级之间存在联系。这些关系的分子机制需要阐明。在我们检测的两个假定的miR-7靶基因中,BCL2而非EGFR似乎是OC中可能的miR-7靶标。