Dirimtekin Esra, Mortoglou Maria, Alavanda Ceren, Benomar Yemlahi Asmaa, Arslan Ates Esra, Guney Ilter, Uysal-Onganer Pinar
Department of Medical Genetics, School of Medicine, Marmara University, 34854 Istanbul, Turkey.
Cancer Mechanisms and Biomarkers Research Group, School of Life Sciences, University of Westminster, W1W 6UW London, U.K.
ACS Omega. 2023 Jul 18;8(30):27743-27750. doi: 10.1021/acsomega.3c03867. eCollection 2023 Aug 1.
Ovarian cancer (OC) is the main cause of gynecological cancer mortality in most developed countries. microRNA (miR) expression dysregulation has been highlighted in human cancers, and miR-34a is found to be downregulated and associated with inhibition of tumor growth and invasion in several malignancies, including OC. The winged helix transcription factor forkhead box P1 (FOXP1) is reported as either an oncogene or tumor suppressor in various cancers. This study aimed to elucidate potential clinical and biological associations of miR-34a and transcription factor FOXP1 in OC. We investigated nine OC patients' blood samples and two OC cell lines (SKOV-3 and OVCAR-3) using quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) to determine both miR-34a and FOXP1 expressions. We have found that miR-34a and FOXP1 are reversely correlated in both in vitro and in vivo. Inhibition of miR-34a transiently led to upregulation of FOXP1 mRNA expression and increased cellular invasion in vitro. Our data indicate that miR-34a could be a potential biomarker for improving the diagnostic efficiency of OC, and miR-34a overexpression may reduce OC pathogenesis by targeting FOXP1.
在大多数发达国家,卵巢癌(OC)是妇科癌症死亡的主要原因。微小RNA(miR)表达失调在人类癌症中已受到关注,并且发现miR-34a在包括OC在内的几种恶性肿瘤中表达下调,且与肿瘤生长和侵袭的抑制相关。有报道称,翼状螺旋转录因子叉头框P1(FOXP1)在各种癌症中既是癌基因又是肿瘤抑制因子。本研究旨在阐明miR-34a与转录因子FOXP1在OC中的潜在临床和生物学关联。我们使用定量实时逆转录聚合酶链反应(RT-qPCR)检测了9例OC患者的血液样本以及两种OC细胞系(SKOV-3和OVCAR-3),以确定miR-34a和FOXP1的表达。我们发现,miR-34a和FOXP1在体外和体内均呈负相关。miR-34a的抑制会短暂导致FOXP1 mRNA表达上调,并增加体外细胞侵袭。我们的数据表明,miR-34a可能是提高OC诊断效率的潜在生物标志物,并且miR-34a的过表达可能通过靶向FOXP1来降低OC的发病机制。