Department of Dermatology, Clinical Center of Spaceport, Chinese PLA General Hospital, Beijing, China.
Department of Dermatology, No. 929 hospital of the Chinese PLA, Shanghai, China.
Neoplasma. 2020 Sep;67(5):1106-1113. doi: 10.4149/neo_2020_190923N954. Epub 2020 Jun 2.
The kelch like family member 22 (KLHL22) is a member of the KLHL (Kelch-like) gene family, which was involved in the progression of breast cancer. However, its role remains unclear in malignant melanoma (MM). Our study found that KLHL22 expression was upregulated in human MM tissues. Regarding the functional analysis for KLHL22 in the progression of MM cells, we demonstrated that overexpression of KLHL22 could promote MM cell growth in vitro. Vice versa, knockdown of KLHL22 could suppress the proliferation of MM cells. Furthermore, KLHL22 also promoted tumorigenesis of MM cells in vivo. In experiments investigating the underlying mechanism, expressions of p-Akt and p-mTOR were significantly increased by overexpression of KLHL22. Meanwhile, knockdown of KLHL22 could decrease the expression levels of p-Akt and p-mTOR. Our studies thus suggest that KLHL22 can promote the growth of MM cells via activating the PI3K/Akt/mTOR signaling pathway, which can serve as a potential target in the diagnosis and/or treatment of MM.
Kelch 样家族成员 22（KLHL22）是 Kelch（Kelch-like）基因家族的成员，该家族参与乳腺癌的进展。然而，其在恶性黑色素瘤（MM）中的作用尚不清楚。我们的研究发现 KLHL22 在人 MM 组织中表达上调。关于 KLHL22 在 MM 细胞进展中的功能分析，我们证明 KLHL22 的过表达可以促进体外 MM 细胞的生长。相反，KLHL22 的敲低可以抑制 MM 细胞的增殖。此外，KLHL22 还促进了 MM 细胞在体内的肿瘤发生。在研究潜在机制的实验中，KLHL22 的过表达显著增加了 p-Akt 和 p-mTOR 的表达。同时，KLHL22 的敲低可以降低 p-Akt 和 p-mTOR 的表达水平。因此，我们的研究表明 KLHL22 可以通过激活 PI3K/Akt/mTOR 信号通路促进 MM 细胞的生长，这可以作为 MM 的诊断和/或治疗的潜在靶点。
