PMID- 32211805 OWN - NLM STAT- MEDLINE DCOM- 20210329 LR - 20210329 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 40 IP - 4 DP - 2020 Apr 30 TI - Knockdown of HSDL2 inhibits lung adenocarcinoma progression via down-regulating AKT2 expression. LID - 10.1042/BSR20200348 [doi] LID - BSR20200348 AB - The aims of the present study are to investigate the role of hydroxysteroid dehydrogenase-like 2 (HSDL2) in the progression of lung adenocarcinoma and illuminate the underlying molecular mechanisms. ShRNA targeting HSDL2 gene (siHSDL2) was utilized to knockdown (KD) HSDL2 expression. In vitro and in vivo experiments were carried out to investigate the effect of siHSDL2 on the progression of lung adenocarcinoma. Microarray hybridization and gene expression analysis were used to investigate effect of siHSDL2 on mRNA expression profile in lung cancer cell line H1299. Our data demonstrated that HSDL2 was up-regulated in lung adenocarcinoma tissue samples (P<0.001). Patients with high HSDL2 expression in cancer tissues had a worse overall survival (P<0.001). HSDL2 KD not only inhibited the proliferation, cell cycle, apoptosis, clone-formation, invasion and migration of lung adenocarcinoma cells in vitro (P<0.05), but also suppressed the growth and metastasis in vivo (P<0.05). HSDL2 KD resulted in up-regulation of 681 genes and down-regulation of 276 genes. HSDL2 KD down-regulated the protein expression and phosphorylation of protein kinase B beta (AKT2) (P<0.001 and P<0.001, respectively) and protein expression of baculoviral IAP repeat-containing 3 (BIRC3; P=0.001), and up-regulated the phosphorylation of ERK (P<0.001). Rescue experiments showed that AKT2 overexpression reversed the suppression effect of siHSDL2 on cell proliferation (P<0.001), invasion (P<0.001) and migration (P<0.001) significantly. HSDL2 functions as an oncogene to promote the growth and metastasis of lung adenocarcinoma via promoting the expression of AKT2. CI - (c) 2020 The Author(s). FAU - Shi, Yujia AU - Shi Y AD - Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. AD - Department of Respiratory and Critical Care Medicine, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu Province, China. FAU - Mao, Zhengdao AU - Mao Z AD - Department of Respiratory and Critical Care Medicine, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu Province, China. FAU - Huang, Yanhua AU - Huang Y AD - Department of Respiratory and Critical Care Medicine, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu Province, China. FAU - Sun, Yun AU - Sun Y AD - Department of Respiratory and Critical Care Medicine, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu Province, China. FAU - Cao, Qi AU - Cao Q AD - Department of Respiratory and Critical Care Medicine, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu Province, China. FAU - Yin, Xiaowei AU - Yin X AD - Department of Respiratory and Critical Care Medicine, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu Province, China. FAU - Huang, Jianan AU - Huang J AD - Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. FAU - Zhang, Qian AU - Zhang Q AD - Department of Respiratory and Critical Care Medicine, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu Province, China. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Small Interfering) RN - EC 1.1.- (HSDL2 protein, human) RN - EC 1.1.- (Hydroxysteroid Dehydrogenases) RN - EC 2.7.11.1 (AKT2 protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Adenocarcinoma of Lung/*genetics/mortality/pathology/surgery MH - Apoptosis/genetics MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Disease Progression MH - Down-Regulation MH - Female MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Humans MH - Hydroxysteroid Dehydrogenases/genetics/*metabolism MH - Immunohistochemistry MH - Lung/pathology/surgery MH - Lung Neoplasms/*genetics/mortality/pathology/surgery MH - Male MH - Middle Aged MH - Neoplasm Invasiveness/genetics/pathology MH - Pneumonectomy MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA, Small Interfering/metabolism MH - Up-Regulation PMC - PMC7138907 OTO - NOTNLM OT - gene chip OT - hydroxysteroid dehydrogenase-like 2 OT - lung adenocarcinoma OT - non-small cell lung cancer OT - prognosis COIS- The authors declare that there are no competing interests associated with the manuscript. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University and with the 1964 Helsinki Declaration and its later amendments. The signed informed consents of all participants were obtained. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. EDAT- 2020/03/27 06:00 MHDA- 2021/03/30 06:00 PMCR- 2020/04/07 CRDT- 2020/03/27 06:00 PHST- 2020/02/14 00:00 [received] PHST- 2020/03/24 00:00 [revised] PHST- 2020/03/24 00:00 [accepted] PHST- 2020/03/27 06:00 [pubmed] PHST- 2021/03/30 06:00 [medline] PHST- 2020/03/27 06:00 [entrez] PHST- 2020/04/07 00:00 [pmc-release] AID - 222464 [pii] AID - BSR20200348 [pii] AID - 10.1042/BSR20200348 [doi] PST - ppublish SO - Biosci Rep. 2020 Apr 30;40(4):BSR20200348. doi: 10.1042/BSR20200348.