PMID- 33860045 OWN - NLM STAT- MEDLINE DCOM- 20210525 LR - 20240226 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2021 DP - 2021 TI - Human Schlafen 5 Inhibits Proliferation and Promotes Apoptosis in Lung Adenocarcinoma via the PTEN/PI3K/AKT/mTOR Pathway. PG - 6628682 LID - 10.1155/2021/6628682 [doi] LID - 6628682 AB - 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. CI - Copyright (c) 2021 Xuefeng Gu et al. FAU - Gu, Xuefeng AU - Gu X AD - Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China. AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China. FAU - Zhou, Li AU - Zhou L AD - Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China. FAU - Chen, Lei AU - Chen L AD - Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China. AD - Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Pan, Huiqing AU - Pan H AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China. FAU - Zhao, Rui AU - Zhao R AD - Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China. AD - Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Guang, Weiwei AU - Guang W AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China. FAU - Wan, Guoqing AU - Wan G AD - Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China. AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China. FAU - Zhang, Peng AU - Zhang P AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China. FAU - Liu, Dingsheng AU - Liu D AD - Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China. FAU - Deng, Li-Li AU - Deng LL AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. FAU - Zhao, Weiming AU - Zhao W AD - Qiqihar Medical University, Qiqihar, Heilongjiang, China. FAU - Lu, Changlian AU - Lu C AUID- ORCID: 0000-0002-0812-9162 AD - Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China. AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20210323 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Cell Cycle Proteins) RN - 0 (SLFN5 protein, human) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) SB - IM RIN - Biomed Res Int. 2024 Jan 9;2024:9767180. PMID: 38230125 MH - A549 Cells MH - Adenocarcinoma of Lung/genetics/metabolism/*pathology MH - Animals MH - *Apoptosis MH - Cell Cycle Proteins/*metabolism MH - Cell Proliferation MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Glycogen Synthase Kinase 3 beta/metabolism MH - Humans MH - Lung Neoplasms/genetics/metabolism/*pathology MH - Mice, Nude MH - PTEN Phosphohydrolase/*metabolism MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism MH - Transcription, Genetic MH - Mice PMC - PMC8009730 COIS- The authors have declared that no competing interest exists. EDAT- 2021/04/17 06:00 MHDA- 2021/05/26 06:00 PMCR- 2021/03/23 CRDT- 2021/04/16 06:40 PHST- 2020/12/08 00:00 [received] PHST- 2021/01/06 00:00 [revised] PHST- 2021/01/21 00:00 [accepted] PHST- 2021/04/16 06:40 [entrez] PHST- 2021/04/17 06:00 [pubmed] PHST- 2021/05/26 06:00 [medline] PHST- 2021/03/23 00:00 [pmc-release] AID - 10.1155/2021/6628682 [doi] PST - epublish SO - Biomed Res Int. 2021 Mar 23;2021:6628682. doi: 10.1155/2021/6628682. eCollection 2021.