致癌性miR-1825通过靶向FREM1促进头颈部癌症的发生
Oncogenic miR-1825 promotes head and neck carcinogenesis via targeting FREM1.
发表日期:2023 Sep 08
作者:
Ozel Capik, Betul Gundogdu, Arzu Tatar, Abdulkadir Sahin, Fengju Chen, Chad J Creighton, Omer Faruk Karatas
来源:
Stem Cell Research & Therapy
摘要:
头颈部鳞状细胞癌(HNSCC)是全球第六常见的恶性肿瘤类型。虽然目前用于HNSCC患者的治疗方法在近几十年来有所改善,但HNSCC的预后仍然较差。因此,迫切需要了解HNSCC的发病机制,开发新颖有效的治疗策略,并鉴定和鉴别对HNSCC恶性表型负责的癌基因。本研究旨在更好地理解miR-1825在HNSCC发病机制中的作用。我们通过体外实验评估细胞存活能力、克隆性、细胞迁移、侵袭、凋亡和干细胞特性,研究了miR-1825失调对与癌症相关的表型的影响。此外,我们还利用裸鼠模型研究了miR-1825过表达对头颈癌细胞肿瘤形成能力的影响。我们使用微阵列分析和荧光素酶活性分析寻找miR-1825的潜在靶标。我们发现,与相应的对照相比,miR-1825在头颈细胞和临床肿瘤样本中的表达上调,可能起到癌基因的作用。然后,我们证明外源性miR-1825过表达在体外促进了与头颈癌进展相关的细胞表型,并在体内对肿瘤形成具有刺激作用。我们还通过免疫组化分析鉴定了FREM1作为miR-1825的直接靶标,并证明其在HNSCC样本中表达减少。总之,我们认为miR-1825/FREM1轴是HNSCC发展的重要调节因子,在其中miR-1825起到了癌基因的作用。© 2023作者。《细胞生物化学杂志》由Wiley Periodicals LLC出版。
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant cancer type worldwide. Although the therapeutic modalities currently used for patients with HNSCC improved in recent decades, HNSCC prognosis is still poor. Therefore, it is an urgent necessity to understand the pathogenesis of HNSCC, to develop novel and effective treatment strategies, and to characterize and identify the oncogenes that are responsible for an aggressive HNSCC phenotype. In this study, we aimed to better understand the roles of miR-1825 in the pathogenesis of HNSCC. We examined the impacts of miR-1825 deregulation on the cancer-associated phenotypes using in vitro tests evaluating cell viability, clonogenicity, cell migration, invasion, apoptosis, and stem cell characteristics. In addition, we investigated the effects of miR-1825 overexpression on the tumor formation capacity of head and neck cancer cells in vivo using nude mice. We searched for potential targets of miR-1825 using microarray analysis and luciferase assay. We found that miR-1825 expression is upregulated in head and neck cells and clinical tumor samples in comparison to corresponding controls, where it potentially acts as an oncogene. We, then, showed that ectopic miR-1825 overexpression promotes cellular phenotypes related to head and neck cancer progression in vitro and has a stimulating potential on cancer formation in vivo. We also identified FREM1 as a direct target of miR-1825 and demonstrated its reduced expression in HNSCC samples using immunohistochemistry analysis. Collectively, we suggest that the miR-1825/FREM1 axis serves as an important mediator of HNSCC development, where miR-1825 acts as an oncogene.© 2023 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC.