Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China.
Department of Head and Neck Surgery, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
J Cell Physiol. 2020 Feb;235(2):1850-1865. doi: 10.1002/jcp.29102. Epub 2019 Jul 23.
The kidney ankyrin repeat-containing protein 1 (Kank1) gene is one of the most important members of the KANK family. Kank1 has hybridity deletion and promoter methylation in the cancer tissues of the brain, lung, kidney and the corresponding cell lines, leading to downregulation of the gene expression. Meanwhile, Kank1 also plays a key role in the occurrence and development of various types of tumors, suggesting that Kank1 may be an anti-oncogene. However, its role and the potential mechanisms in the Oral Squamous Cell Carcinoma (OSCC) remain unclear. We examined the expression of Kank1 in OSCC tissues and explored its clinical significance. In addition, we investigated the effects of Kank1 on the biological behavior of OSCC cells and their specific molecular mechanisms. We found that Kank1 was poorly expressed in OSCC tissues and it is correlated with the OSCC stage and the patient's poor prognosis. By overexpression of Kank1, we found that the proliferation ability of the OSCC cells decreased both in vitro and in vivo, the proportion of apoptotic cells increased, and the mitochondrial transmembrane potential decreased. In terms of the molecular mechanism, we confirmed that Kank1 could inhibit the occurrence of OSCC by regulating Yap to inhibit the proliferation and promote apoptosis of the OSCC cells. Moreover, it was found that the overexpression of YAP reversed those effects caused by Kank1 overexpression on the OSCC cells. In conclusion, the research indicated that Kank1 might play an anti-oncogenic role in OSCC and it could be considered to be a target for the diagnosis and the treatment of OSCC.
肾脏锚蛋白重复蛋白 1（Kank1）基因是 KANK 家族中最重要的成员之一。Kank1 在脑、肺、肾和相应细胞系的癌症组织中存在杂交缺失和启动子甲基化，导致基因表达下调。同时，Kank1 在各种类型肿瘤的发生和发展中也起着关键作用，表明 Kank1 可能是一种抑癌基因。然而，其在口腔鳞状细胞癌（OSCC）中的作用及其潜在机制尚不清楚。我们检测了 Kank1 在 OSCC 组织中的表达情况，并探讨了其临床意义。此外，我们还研究了 Kank1 对 OSCC 细胞生物学行为的影响及其特定的分子机制。我们发现 Kank1 在 OSCC 组织中表达水平较低，且与 OSCC 分期和患者预后不良相关。通过过表达 Kank1，我们发现 OSCC 细胞的体外和体内增殖能力均降低，凋亡细胞比例增加，线粒体跨膜电位降低。在分子机制方面，我们证实 Kank1 可以通过调节 Yap 抑制 OSCC 的发生，从而抑制 OSCC 细胞的增殖并促进其凋亡。此外，还发现 YAP 的过表达逆转了 Kank1 过表达对 OSCC 细胞产生的上述作用。综上所述，该研究表明 Kank1 可能在 OSCC 中发挥抑癌作用，可考虑将其作为 OSCC 诊断和治疗的靶点。
