PMID- 28893265 OWN - NLM STAT- MEDLINE DCOM- 20180524 LR - 20231213 IS - 1476-4598 (Electronic) IS - 1476-4598 (Linking) VI - 16 IP - 1 DP - 2017 Sep 11 TI - Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. PG - 151 LID - 10.1186/s12943-017-0719-3 [doi] LID - 151 AB - BACKGROUND: Non-coding RNAs (ncRNAs) have been shown to regulate gene expression involved in tumor progression of multiple malignancies. Our previous studies indicated that large tumor suppressor kinase 1 (LATS1), a core part of Hippo signaling pathway, functions as a tumor suppressor in gastric cancer (GC). But, the underlying molecular mechanisms by which ncRNAs modulate LATS1 expression in GC remain undetermined. METHODS: The correlation of LATS1 and has-miR-424-5p (miR-424) expression with clinicopathological characteristics and prognosis of GC patients was analyzed by TCGA RNA-sequencing data. A novel circular RNA_LARP4 (circLARP4) was identified to sponge miR-424 by circRNA expression profile and bioinformatic analysis. The binding site between miR-424 and LATS1 or circLARP4 was verified using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The expression and localization of circLARP4 in GC tissues were investigated by fluorescence in situ hybridization (FISH). MTT, colony formation, Transwell and EdU assays were performed to assess the effects of miR-424 or circLARP4 on cell proliferation and invasion. RESULTS: Increased miR-424 expression or decreased LATS1 expression was associated with pathological stage and unfavorable prognosis of GC patients. Ectopic expression of miR-424 promoted proliferation and invasion of GC cells by targeting LATS1 gene. Furthermore, circLARP4 was mainly localized in the cytoplasm and inhibited biological behaviors of GC cells by sponging miR-424. The expression of circLARP4 was downregulated in GC tissues and represented an independent prognostic factor for overall survival of GC patients. CONCLUSION: circLARP4 may act as a novel tumor suppressive factor and a potential biomarker in GC. FAU - Zhang, Jing AU - Zhang J AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Liu, Hui AU - Liu H AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Hou, Lidan AU - Hou L AD - Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Ge AU - Wang G AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Zhang, Rui AU - Zhang R AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Huang, Yanxia AU - Huang Y AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Chen, Xiaoyu AU - Chen X AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Zhu, Jinshui AU - Zhu J AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. zhujs1803@163.com. LA - eng PT - Journal Article DEP - 20170911 PL - England TA - Mol Cancer JT - Molecular cancer JID - 101147698 RN - 0 (Autoantigens) RN - 0 (Biomarkers, Tumor) RN - 0 (MIRN424 microrna, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (Ribonucleoproteins) RN - 63231-63-0 (RNA) RN - EC 2.7.1.- (LATS1 protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Autoantigens/*genetics MH - Biomarkers, Tumor MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Cell Survival/genetics MH - Ectopic Gene Expression MH - Gene Expression Profiling MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - MicroRNAs/*genetics MH - Neoplasm Grading MH - Neoplasm Invasiveness MH - Neoplasm Staging MH - Prognosis MH - Protein Serine-Threonine Kinases/*genetics MH - RNA/*genetics MH - RNA Interference MH - RNA, Circular MH - ROC Curve MH - Reproducibility of Results MH - Ribonucleoproteins/*genetics MH - Stomach Neoplasms/*genetics/mortality/*pathology MH - SS-B Antigen PMC - PMC5594516 OTO - NOTNLM OT - Circular RNA_LARP4 OT - Gastric cancer OT - Invasion OT - LATS1 OT - miR-424-5p COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The present study was approved by the Hospital's Protection of Human Subjects Committee. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/09/13 06:00 MHDA- 2018/05/25 06:00 PMCR- 2017/09/11 CRDT- 2017/09/13 06:00 PHST- 2017/05/25 00:00 [received] PHST- 2017/08/31 00:00 [accepted] PHST- 2017/09/13 06:00 [entrez] PHST- 2017/09/13 06:00 [pubmed] PHST- 2018/05/25 06:00 [medline] PHST- 2017/09/11 00:00 [pmc-release] AID - 10.1186/s12943-017-0719-3 [pii] AID - 719 [pii] AID - 10.1186/s12943-017-0719-3 [doi] PST - epublish SO - Mol Cancer. 2017 Sep 11;16(1):151. doi: 10.1186/s12943-017-0719-3.