Background: Tongue squamous cell carcinoma (TSCC) is the second most common malignancy in oral carcinoma. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1 ) was regarded as an oncogenic factor in various carcinomas. However, its underlying molecular mechanisms in the development and progression of TSCC have not been well featured till now. 
Methods: The expressions of MALAT1 , miR-140-5p  and p21 (RAC1)-activated kinase 1 (PAK1) mRNA were measured by RT-qPCR assay. The protein level of PAK1 was determined by western blot analysis. Cell viability was detected by Cell Counting Kit-8 assay. Transwell chamber was used to detect cell migratory and invasive capability. Luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and biotin pull-down assay were applied to evaluate the relationship between MALAT1 , miR-140-5p  and PAK1. Xenograft experiments were performed to assess the effect and mechanism of MALAT1  in TSCC tumor growth.
Results: The expression of MALAT1  and p21 (RAC1)-activated kinase 1 (PAK1) was upregulated and microRNA-140-5p (miR-140-5p ) expression was downregulated in TSCC tissues and cells. MALAT1  knockdown induced miR-140-5p  expression by direct interaction. Moreover, MALAT1  knockdown inhibited proliferation, migration, and invasion by upregulating miR-140-5p  expression in TSCC cells. Additionally, PAK1 was identified as a direct target of miR-140-5p . Also, MALAT1  knockdown inhibited PAK1 expression by upregulating miR-140-5p  in TSCC cells. Furthermore, miR-140-5p  overexpression curbed the proliferation, migration, and invasion of TSCC cells by targeting PAK1. Finally, MALAT1  knockdown inhibited tumor growth by upregulating miR-140-5p  and downregulating PAK1 in mouse xenograft models of TSCC. 
Conclusion: MALAT1  contributed to TSCC progression via miR-140-5p -PAK1 regulatory axis, highlighting a potential target for TSCC management.
Keywords: tongue squamous cell carcinoma, lncRNA, MALAT1 , miRNA-140-5p, PAK1