Ercoşkun Pelin, Ağirbaşli Deniz, Velidedeoğlu Mehmet, Seven Mehmet, Kalayci Aysel
Department of Medical Genetics, Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Turkiye.
Department of General Surgery, Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Turkiye.
Turk J Med Sci. 2025 May 30;55(3):782-791. doi: 10.55730/1300-0144.6027. eCollection 2025.
BACKGROUND/AIM: Several epigenetic alterations are involved in the development of breast cancer. The long noncoding RNA HOTAIR and related RNAs play a role in initiation of breast cancer and are promising targets for diagnostic biomarker and therapeutic studies. In this study, we aimed to investigate associated ceRNA HOTAIR pathway in breast cancer patients.
Forty breast cancer patients and ten healthy controls were included in this study, and then patients were divided into clinicopathologic groups. After total cell-free RNA isolation, expression levels of target RNAs were analysed by Real-Time PCR. The amount of gene expression was determined according to delta-delta Ct method and change in the expression was determined using the 2 method.
HOTAIR expression was significantly higher in the study group (especially in the ER negative group) than in the control group (p value = 0.006). When patients with relapse were compared with those without relapse, expression was significantly higher (p value = 0.048). There was a significant increase in miR-20a-5p expression (p value = 0.002) in the premenopausal group compared to the postmenopausal group, while there was a significant decrease in expression (p value = 0.002). A positive correlation between patient age and and a negative correlation between patient age and miR-20a-5p were found (respectively p value: 0.037 and p value: 0.006. Also, we found a negative correlation between and miR-20a-5p (p value: 0.027, correlation coefficient: -0.350).
To our knowledge, this study is the first to examine the association of the associated HOTAIR axis with breast cancer in cell-free RNA from peripheral blood of patients. Our findings emphasize the potential of the associated HOTAIR axis as a prognostic biomarker and therapeutic target, especially in ER negative, postmenopausal onset, and relapsed breast cancer.
背景/目的:多种表观遗传改变参与乳腺癌的发生发展。长链非编码RNA HOTAIR及相关RNA在乳腺癌的起始过程中发挥作用,是诊断生物标志物和治疗研究的有前景的靶点。在本研究中,我们旨在探究乳腺癌患者中相关的竞争性内源性RNA(ceRNA)HOTAIR通路。
本研究纳入40例乳腺癌患者和10例健康对照,然后将患者分为临床病理组。在分离出全部无细胞RNA后,通过实时定量聚合酶链反应(Real-Time PCR)分析靶RNA的表达水平。基因表达量根据ΔΔCt法确定,表达变化使用2−ΔΔCt法确定。
研究组(尤其是雌激素受体(ER)阴性组)中HOTAIR的表达显著高于对照组(p值 = 0.006)。将复发患者与未复发患者进行比较时,HOTAIR的表达显著更高(p值 = 0.048)。与绝经后组相比,绝经前组中miR-20a-5p的表达显著增加(p值 = 0.002),而HOTAIR的表达显著降低(p值 = 0.002)。发现患者年龄与HOTAIR呈正相关,与miR-20a-5p呈负相关(p值分别为0.037和0.006)。此外,我们发现HOTAIR与miR-20a-5p呈负相关(p值:0.027,相关系数:−0.350)。
据我们所知,本研究首次在外周血无细胞RNA中检测相关的HOTAIR轴与乳腺癌的关联。我们的研究结果强调了相关的HOTAIR轴作为预后生物标志物和治疗靶点的潜力,尤其是在ER阴性、绝经后发病和复发的乳腺癌中。