Recently, increasing evidences have proved that the aberrant expression of lncRNAs might facilitate to the development and progression of solid tumors and particular lncRNAs were identified as independent biomarker [17–19]. Due to the unknown biological functions of lncRNAs and limited understand of the molecular mechanisms, more studies are needed. Our present study investigated an OSCC prognosis-related lncRNA—-linc01234, and elucidated its functional roles in OSCC progression.
In the present research, we found that linc01234 was significantly upregulated in clinical OSCC samples and numerous OSCC cell lines. High expressed linc01234 was positively related to advanced T stage, lymph node metastasis and poor pathological differentiation. In addition, OSCC patients with high linc01234 expression had a worse OS than patients with low linc01234 expression based on Starbase database analysis. Cox analysis also indicated that linc01234 expression could be an independent predictor for OSCC patients’ prognosis as well as T stage, N stage and advanced pathological stage. In biological functional experiments, linc01234 inhibition prominently contributed to the decreased proliferative activity and metastasis in CAL27 and SCC25 cells. In summary, our results suggested that linc01234 plays a cancer-promoting role in cell growth and metastasis in OSCC.
Growing evidences indicated that lncRNAs and mRNAs could cross regulate each other via competing for shared miRNA response elements (MREs) [16,20]. Specifically, many lncRNAs act as a sponge in the regulation of miRNA target gene involving OSCC carcinogenesis [21,22]. miR‐433, a well-characterized miRNA, was found as a tumor suppresser in different neoplasms [23,24]. Furthermore, Wang et al reported that miR‐433 was downregulated in OSCC tissues and evaluated miR–433 expression markedly suppressed cells proliferation, invasion and migration through targeting HDAC6 [25]. In our study, we found that linc01234 contained miRNA response elements for miR–433–3p with a 13nt complementarity. Dual-luciferase assays confirmed a direct correlation between miR‐433–3p and linc01234. RT‐PCR results showed that linc01234 deletion increased the expression levels of miR‐433–3p, which was dramatically downregulated in HNSCC tissues. Our data suggested that linc01234 exerted its function through competing with miR‐433–3p in OSCC. However, the underlying mechanism of linc01234/miR–433–3p axis regulating OSCC progression is still unclear.
p21-Activated kinase 4 (PAK4), a member of the PAK family, regulates a wide range of cellular functions, including cell adhesion, migration, proliferation, and survival [26,27]. Previous studies have reported that dysregulation of PAK4 expression contributes to development and progression of various tumors [28,29]. Several studies have reported that PAK4 could be regulated by many miRNAs in various cancers, including miR–485, miR–199a–3p [30–32]. Especially, in OSCC, PAK4 served as an SE-associated candidate oncogene and promoted the proliferation of OSCC cells [33]. In our study, we screened PAK4 as a potential target gene of miR‐433–3p based on Starbase prediction. Dual‐luciferase assay have confirmed that miR–433–3p bind to PAK4 directly. Furthermore, PAK4 protein levels in CAL27 and SCC25 cells with miR‐433–3p overexpression were significantly inhibited. Overall, our founding suggested that linc01234 modulated OSCC carcinogenesis through miR‐433–3p-mediated PAK4.