Chen Zhifeng, Tao Qian, Qiao Bin, Zhang Leitao
Department of Oral and Maxillofacial Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, People's Republic of China.
Cancer Manag Res. 2019 Jul 3;11:6043-6059. doi: 10.2147/CMAR.S197583. eCollection 2019.
Oral squamous cell carcinoma (OSCC), one of the most common cancers worldwide with a high mortality rate, is accompanied by poor prognosis, highlighting the significance of early diagnosis and effective treatment. Long non-coding RNAs (lncRNAs) have been linked with the development and progression of various cancers. In this study, aberrantly expressed lncRNA LINC01116, microRNA-136 (miR-136), and fibronectin1 (FN1) were identified in OSCC using a microarray analysis. Therefore, this study aimed to investigate the role of LINC01116/miR-136/FN1 regulatory axis in OSCC.
The gain-of-function and loss-of-function experiments in vitro were performed to alter the expression of LINC01116 and miR-136 in OSCC cells to elucidate their effects on cellular processes, including epithelial-mesenchymal transition (EMT), viability, invasion, and migration. In addition, the interaction among LINC01116, miR-136, and FN1 was identified. Additionally, the tumorigenicity and lymph node metastasis (LNM) affected by LINC01116 were observed through xenograft tumor in nude mice.
LINC01116 and FN1 were abundant in both OSCC tissues and cells, while miR-136 was poorly expressed. LINC01116 could competitively bind to miR-136, which targets and negatively regulates FN1. Moreover, in response to LINC01116 silencing or miR-136 over-expression, OSCC cells exhibited diminished EMT process and inhibited cell viability, invasion, and migration in vitro, coupling with impaired tumorigenicity and LNM in vivo.
The fundamental findings in this study collectively demonstrate that LINC01116 silencing may inhibit the progression of OSCC the miR-136-mediated FN1 inhibition, highlighting a promising therapeutic strategy for OSCC treatment.
口腔鳞状细胞癌（OSCC）是全球最常见的癌症之一，死亡率高，预后较差，这凸显了早期诊断和有效治疗的重要性。长链非编码RNA（lncRNA）与多种癌症的发生和发展有关。在本研究中，通过微阵列分析在OSCC中鉴定出异常表达的lncRNA LINC01116、微小RNA-136（miR-136）和纤连蛋白1（FN1）。因此，本研究旨在探讨LINC01116/miR-136/FN1调控轴在OSCC中的作用。
进行体外功能获得和功能丧失实验，以改变OSCC细胞中LINC01116和miR-136的表达，阐明它们对细胞过程的影响，包括上皮-间质转化（EMT）、活力、侵袭和迁移。此外，还鉴定了LINC01116、miR-136和FN1之间的相互作用。另外，通过裸鼠异种移植瘤观察LINC01116对肿瘤发生和淋巴结转移（LNM）的影响。
LINC01116和FN1在OSCC组织和细胞中均大量存在，而miR-136表达较低。LINC01116可以竞争性结合miR-136，而miR-136靶向并负调控FN1。此外，在LINC01116沉默或miR-136过表达后，OSCC细胞在体外表现出EMT过程减弱，细胞活力、侵袭和迁移受到抑制，同时在体内肿瘤发生和LNM受损。
本研究的基本发现共同表明，LINC01116沉默可能通过miR-136介导的FN1抑制作用来抑制OSCC的进展，为OSCC治疗提供了一种有前景的治疗策略。
