Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related death worldwide and therefore a serious public health concern [1]. Many patients with OSCC develop metastasis and recurrence, regardless of the treatment or the location, size, or stage of the tumor [2], [3]. Tumor recurrence and distant metastasis are the major causes of death in patients, particularly of those diagnosed with OSCC in the advanced stage [4]. Previously identified markers of OSCC metastasis or recurrence have not been validated [5], [6]. Further, exosomal long noncoding RNAs (lncRNAs), which are biomarkers in other diseases, have not been investigated in OSCC.

Noncoding RNAs (ncRNAs) mainly include microRNAs (miRNAs),and lncRNAs [7]. miRNAs contain 19–25 nucleotides, while lncRNAs contain over 200 nucleotides, respectively [8]. ncRNAs cannot encode proteins or peptides, but regulate gene expressions via several mechanisms [9]. The abnormal expression of the noncoding genome, including mutations in protein-coding genes, results in some tumor phenotypes.

Exosomes are small membranous vesicles that are released from intracellular multivesicular bodies, with their diameter ranging from 30 to 120 nm [10]. They are found in most body fluids of humans, such as blood, abdominal fluid, urine, and saliva [10]. Exosomal content includes proteins, DNAs, and RNAs. Exosome-derived miRNAs promote OSCC metastasis, possibly by means of altering intercellular communications [11]. Exosomes transport functional lncRNAs intercellularly, and lncRNAs and exosomes function together to perform cell signal transmission, which modulates the relocation of the intercellular microenvironment [12].

Some lncRNAs are related to the development of OSCC [13], [14] and affect the proliferation, migration, invasion abilities, and apoptosis of OSCC cells [15], [16]. Thus, exosomal lncRNAs could be diagnostic and prognostic indicators and therapeutic and prognostic targets in OSCC [17], [18], [19]. The aim of this case–control study was to investigate the effectiveness of exosomal lncRNAs as a diagnostic indicator of OSCC with and without lymph node metastasis (OSCC-LNM and OSCC-NLNM, respectively) and recurrent OSCC (rOSCC). Additionally, we aimed to explore the roles played by MAGI2-AS3 and CCDC144NL-AS1 in OSCC cells, focusing on investigating the novel molecular mechanism underlying their involvement in OSCC cell growth, migration, and invasion.