PMID- 31160270 OWN - NLM STAT- MEDLINE DCOM- 20191218 LR - 20210117 IS - 2352-3964 (Electronic) IS - 2352-3964 (Linking) VI - 44 DP - 2019 Jun TI - The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p. PG - 182-193 LID - S2352-3964(19)30340-8 [pii] LID - 10.1016/j.ebiom.2019.05.032 [doi] AB - BACKGROUND: Non-small cell lung carcinomas (NSCLC) are prevalent, lethal cancers with especially grim prospects due to late-stage detection and chemoresistance. Circular RNAs (circRNAs) are non-coding RNAs that participate in tumor development. However, the role of circRNAs in NSCLC is not well known. This study investigated the role of one circRNA - circPTPRA- in NSCLC and characterized its molecular mechanism of action. METHODS: circPTPRA expression was analyzed in human NSCLC tumors and matched healthy lung tissue. We performed functional characterization in NSCLC cell lines and a mouse xenograft model of NSCLC to elucidate the molecular role of circPTPRA in epithelial-mesenchymal transitioning (EMT). We also assessed the regulatory action of circPTPRA on the microRNA miR-96-5p and its target the tumor suppressor Ras association domain-containing protein 8 (RASSF8). FINDINGS: circPTPRA was significantly downregulated in NSCLC tumors relative to matched healthy lung tissue. Lower circPTPRA levels correlated with metastasis and inferior survival outcomes in NSCLC patients. circPTPRA suppressed EMT in NSCLC cell lines and reduced metastasis in the murine xenograft model by sequestering miR-96-5p and upregulating RASSF8. Correlation analyses in patient-derived NSCLC tumor specimens supported the involvement of the circPTPRA/miR-96-5p/RASSF8/E-cadherin axis dysregulation in NSCLC tumor progression. INTERPRETATION: circPTPRA suppresses EMT and metastasis of NSCLC cell lines by sponging miR-96-5p, which upregulates the downstream tumor suppressor RASSF8. The circPTPRA/miR-96-5p/RASSF8/E-cadherin axis can be leveraged as a potential treatment avenue in NSCLC. FUND: The Key research and development projects of Anhui Province (201904a0720079), the Natural Science Foundation of Anhui Province (1908085MH240), the Graduate Innovation Program of Bengbu Medical College (Byycx1843), the National Natural Science Foundation of Tibet (XZ2017ZR-ZY033) and the Science and Technology Project of Shannan (SNKJYFJF2017-3) and Academic Subsidy Project for Top Talents in Universities of Anhui in 2019 (gxbjZD16). CI - Copyright (c) 2019 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Wei, Siliang AU - Wei S AD - Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China. FAU - Zheng, Yuanyuan AU - Zheng Y AD - Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China. FAU - Jiang, Yanru AU - Jiang Y AD - Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China. FAU - Li, Xiaojun AU - Li X AD - Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China. FAU - Geng, Jian AU - Geng J AD - Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233004, China; Anhui Province Key Laboratory of Translational Cancer Research, 233004, China. FAU - Shen, Yuanbing AU - Shen Y AD - Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China. FAU - Li, Qin AU - Li Q AD - Department of Respiratory Disease, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China. FAU - Wang, Xiaojing AU - Wang X AD - Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China. FAU - Zhao, Chengling AU - Zhao C AD - Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China. FAU - Chen, Yuqing AU - Chen Y AD - Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China. FAU - Qian, Zhongqing AU - Qian Z AD - Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, Anhui 233003, China. FAU - Zhou, Jihong AU - Zhou J AD - Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233004, China; Anhui Province Key Laboratory of Translational Cancer Research, 233004, China. Electronic address: zhoujihongww@126.com. FAU - Li, Wei AU - Li W AD - Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China; Anhui Province Key Laboratory of Translational Cancer Research, 233004, China. Electronic address: bbmcliwei@126.com. LA - eng PT - Journal Article DEP - 20190531 PL - Netherlands TA - EBioMedicine JT - EBioMedicine JID - 101647039 RN - 0 (Cadherins) RN - 0 (MIRN96 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - EC 3.1.3.48 (PTPRA protein, human) RN - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4) SB - IM MH - Animals MH - Cadherins/genetics/metabolism MH - Carcinoma, Non-Small-Cell Lung/*genetics/mortality/*pathology/therapy MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Epithelial-Mesenchymal Transition/*genetics MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*genetics/mortality/*pathology/therapy MH - Mice MH - MicroRNAs/*genetics MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Phenotype MH - RNA Interference MH - RNA, Circular/*genetics MH - Receptor-Like Protein Tyrosine Phosphatases, Class 4/*genetics PMC - PMC6604667 OTO - NOTNLM OT - Epithelial-mesenchymal transition, EMT OT - Lung cancer OT - NSCLC OT - circRNA OT - miR-96-5p EDAT- 2019/06/05 06:00 MHDA- 2019/12/19 06:00 PMCR- 2019/05/31 CRDT- 2019/06/05 06:00 PHST- 2019/02/21 00:00 [received] PHST- 2019/05/06 00:00 [revised] PHST- 2019/05/13 00:00 [accepted] PHST- 2019/06/05 06:00 [pubmed] PHST- 2019/12/19 06:00 [medline] PHST- 2019/06/05 06:00 [entrez] PHST- 2019/05/31 00:00 [pmc-release] AID - S2352-3964(19)30340-8 [pii] AID - 10.1016/j.ebiom.2019.05.032 [doi] PST - ppublish SO - EBioMedicine. 2019 Jun;44:182-193. doi: 10.1016/j.ebiom.2019.05.032. Epub 2019 May 31.