Department of Oncology, Molecular Oncology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350000, China.
Department of Oncology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
Epigenetics. 2023 Dec;18(1):2175168. doi: 10.1080/15592294.2023.2175168. Epub 2023 Feb 3.
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 to be overexpressed in HNSCC. According to bioinformatics analysis, apoptosis and P53 pathways were remarkably enriched in the 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.
头颈部鳞状细胞癌（HNSCC）仍然是一种恶性肿瘤，临床疗效不佳，越来越多的证据表明 RNA 结合蛋白（RBPs）与疾病的发展有关。KHDC1 家族作为 RBPs 的一种，被证明与细胞存活和死亡密切相关。作为一种新型 KHDC1 成员，目前只有一项研究在骨关节炎滑膜细胞中揭示了 KHDC1L 促进增殖的功能。然而，据我们所知，KHDC1L 在人类肿瘤中的作用尚未得到充分探索。基于癌症基因组图谱（TCGA）数据库和细胞系与本研究中正常对照的比较，我们首先发现 KHDC1L 在 HNSCC 中过表达。根据生物信息学分析，在 TCGA 数据库中，低表达组中凋亡和 P53 通路显著富集。此外，体外实验应用于验证 KHDC1L 的上调可促进 HNSCC 细胞 CAL27 的增殖并抑制凋亡。转录组测序确定下游差异表达基因在 PI3K-AKT 通路中显著富集。此外，通过 Western blot 验证，我们发现 KHDC1L 上调组中 pAKT/AKT 和 Bcl-2 的表达水平升高，BAX 的表达水平不变，Caspase-3 和 PARP-1 的活性降低。总之，我们的研究首次阐明，KHDC1L 通过 AKT 和 Bcl-2 通路促进 HNSCC 细胞 CAL27 的增殖和抑制凋亡，代表着在 HNSCC 中寻找新的诊断和治疗靶点的重要一步。
