Head and neck squamous cell carcinoma (HNSCC) remains a dreadful malignancy bearing poor clinical efficacy, with emerging evidences indicating RNA-binding proteins' (RBPs') relevance to the evolution of the disease. Categorized as RBPs, the K-homology domain-containing 1 (KHDC1) family is proved to be closely related to cell survival and death. As a novel KHDC1 member, only one study is currently available in osteoarthritis synovial cells to unveil KHDC1L's function of promoting proliferation. Nevertheless, to the best of our knowledge, the role of KHDC1L in human tumour is yet to be fully explored. On the basis of The Cancer Genome Atlas (TCGA) database and cell lines comparison with normal counterparts in this study, we first discovered KHDC1L to be overexpressed in HNSCC. According to bioinformatics analysis, apoptosis and P53 pathways were remarkably enriched in the KHDC1L low-expression group in TCGA database. Moreover, in vitro experiments were applied to verify that upregulation of KHDC1L could promote the proliferation and inhibit apoptosis in HNSCC cells CAL27. Transcriptome sequencing ascertained downstream differentially expressed genes to be significantly enriched in PI3K-AKT pathways. Furthermore, as validated by western blot, we found an elevated expression level of pAKT/AKT and Bcl-2, constant expression level of BAX, together with decreased activity of Caspase-3 and PARP-1 in the KHDC1L-upregulated group. In conclusion, our study pioneeringly elaborated that KHDC1L could promote proliferation and inhibit apoptosis in HNSCC cell CAL27 via AKT and Bcl-2 pathways, representing a crucial step for seeking a new diagnostic and therapeutic target in HNSCC.
Keywords: AKT; KHDC1L; apoptosis; head and neck squamous cell carcinoma; proliferation.