Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China.
Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China.
Biomed Res Int. 2021 Mar 23;2021:6628682. doi: 10.1155/2021/6628682. eCollection 2021.
Human Schlafen 5 (SLFN5) is reported to inhibit or promote the proliferation of several specific types of cancer cells by our lab and other researchers. We are curious about its implications in lung adenocarcinoma (LUAC), a malignant tumor with a high incidence rate and high mortality.
Lentiviral stable transfections of SLFN5-specific shRNA for knockdown and SLFN5 full-length coding sequence for overexpression were performed in LUAC cell for proliferation analysis in vitro and in vivo in nude mice. Clinical LUAC samples were collected for immunohistochemical analysis of SLFN5 protein levels.
We found that knockdown of endogenous SLFN5 upregulates cancer cell proliferation while inhibiting apoptosis. Besides, SLFN5 inhibition on proliferation was also observed in a nude mouse xenograft model. In contrast, overexpression of exogenous SLFN5 inhibited cell proliferation and and promoted apoptosis. As to the signaling pathway, we found phosphatase and tensin homolog on chromosome 10 (PTEN) was positively regulated by SLFN5, while its downstream signaling pathway AKT/mammalian target of rapamycin (mTOR) was inhibited. Moreover, compared with adjacent normal tissues, SLFN5 protein levels were markedly decreased in lung adenocarcinoma tissues. In conclusion, these suggest that human SLFN5 plays inhibitory roles in LUAC progression through the PTEN/PI3K/AKT/mTOR pathway, providing a potential target for developing drugs for lung cancer therapy in the future.
我们实验室和其他研究人员发现，人类 Schlafen 5（SLFN5）可抑制或促进几种特定类型癌细胞的增殖。我们对其在肺腺癌（LUAC）中的作用感到好奇，LUAC 是一种发病率和死亡率都很高的恶性肿瘤。
通过慢病毒稳定转染 SLFN5 特异性 shRNA 进行敲低和 SLFN5 全长编码序列过表达，在体外和裸鼠体内进行 LUAC 细胞增殖分析。收集临床 LUAC 样本进行 SLFN5 蛋白水平的免疫组织化学分析。
我们发现内源性 SLFN5 的敲低会上调癌细胞增殖，同时抑制细胞凋亡。此外，在裸鼠异种移植模型中也观察到 SLFN5 对增殖的抑制作用。相反，外源性 SLFN5 的过表达抑制细胞增殖并促进细胞凋亡。就信号通路而言，我们发现 SLFN5 可正向调控 10 号染色体磷酸酶和张力蛋白同源物（PTEN），同时抑制其下游信号通路 AKT/哺乳动物雷帕霉素靶蛋白（mTOR）。此外，与相邻正常组织相比，肺腺癌组织中 SLFN5 蛋白水平明显降低。综上所述，这些结果表明，人类 SLFN5 通过 PTEN/PI3K/AKT/mTOR 通路在 LUAC 进展中发挥抑制作用，为未来开发肺癌治疗药物提供了潜在靶点。
