Samadaian Niusha, Salehipour Pouya, Ayati Mohsen, Rakhshani Naser, Najafi Ali, Afsharpad Mandana, Yazarlou Fatemeh, Modarressi Mohammad Hossein
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, 1417613151, Iran.
Department of Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, 1417613151, Iran.
Pathol Res Pract. 2018 Dec;214(12):2018-2024. doi: 10.1016/j.prp.2018.09.019. Epub 2018 Sep 29.
Deregulation of key signaling pathways is one of the primary phenomena in carcinogenesis. DAB2IP and SPRY2 are regulatory elements, which act as feedback inhibitors of receptor tyrosine kinases signaling in mitogen-activated protein kinase pathway. These elements have also been implicated in the pathophysiology of cancer. Therefore, this study is aimed to investigate the expression of all known splice variants of DAB2IP and SPRY2 in prostate tissue. Fresh Prostate tissue samples (50 prostate cancer/ matched normal tissue and 30 BPH) were collected and total RNA was extracted followed by cDNA synthesis. The expression of DAB2IP and SPRY2 transcript variants were evaluated using RT-PCR and quantitative Real-time PCR. The results indicated significant down-regulation of DAB2IP transcript variant 1 in cancerous tissues compared to paired normal tissues (P = 0.001) as well as SPRY2 transcript variant 2 in cancerous tissues in comparison with the normal counterparts and BPH (P = 0.008 and P = 0.025, respectively). In addition, there was a significant negative correlation between DAB2IP.1 and SPRY2.2 expression with PSA levels in prostate cancer (P = 0.039 ρ =-0.24 and P = 0.045 ρ =-0.3, respectively). Interestingly, the down-regulation of DAB2IP.1 mRNA and SPRY2.2 mRNA was positively correlated in tumor samples (P = 0.002 ρ = 0.434). For the first time, this experiment highlights the deregulation of DAB2IP and SPRY2 transcript variants in human prostate cancer. The present study confirms and extends the previous reports through indicating transcript-specific down-regulation and significant association of DAB2IP and SPRY2 in prostate tumorigenesis.
关键信号通路的失调是致癌过程中的主要现象之一。DAB2IP和SPRY2是调控元件,在丝裂原活化蛋白激酶途径中作为受体酪氨酸激酶信号的反馈抑制剂发挥作用。这些元件也与癌症的病理生理学有关。因此,本研究旨在调查DAB2IP和SPRY2所有已知剪接变体在前列腺组织中的表达情况。收集新鲜前列腺组织样本(50例前列腺癌/配对正常组织和30例良性前列腺增生),提取总RNA,随后进行cDNA合成。使用逆转录聚合酶链反应(RT-PCR)和定量实时聚合酶链反应评估DAB2IP和SPRY2转录变体的表达。结果表明,与配对正常组织相比,癌组织中DAB2IP转录变体1显著下调(P = 0.001),与正常组织和良性前列腺增生相比,癌组织中SPRY2转录变体2也显著下调(分别为P = 0.008和P = 0.025)。此外,在前列腺癌中,DAB2IP.1和SPRY2.2的表达与前列腺特异抗原(PSA)水平之间存在显著负相关(分别为P = 0.039,ρ = -0.24和P = 0.045,ρ = -0.3)。有趣的是,在肿瘤样本中,DAB2IP.1 mRNA和SPRY2.2 mRNA的下调呈正相关(P = 0.002,ρ = 0.434)。本实验首次突出了人前列腺癌中DAB2IP和SPRY2转录变体的失调。本研究通过表明转录本特异性下调以及DAB2IP和SPRY2在前列腺肿瘤发生中的显著关联,证实并扩展了先前的报道。