1. Human Schlafen 5 Inhibits Proliferation and Promotes Apoptosis in Lung Adenocarcinoma via the PTEN/PI3K/AKT/mTOR Pathway.
- Author
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Gu, Xuefeng, Zhou, Li, Chen, Lei, Pan, Huiqing, Zhao, Rui, Guang, Weiwei, Wan, Guoqing, Zhang, Peng, Liu, Dingsheng, Deng, Li-Li, Zhao, Weiming, and Lu, Changlian
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ADENOCARCINOMA , *LUNG cancer , *BIOLOGICAL models , *IN vitro studies , *DISEASE progression , *IN vivo studies , *XENOGRAFTS , *ANIMAL experimentation , *IMMUNOHISTOCHEMISTRY , *APOPTOSIS , *CELL cycle proteins , *PHOSPHATASES , *CELLULAR signal transduction , *GENE expression , *CELL proliferation , *PHOSPHOPROTEINS , *MICE - Abstract
Background. 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. Method. 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. Results. 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 in vitro and in vivo 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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