PMID- 30755230 OWN - NLM STAT- MEDLINE DCOM- 20190624 LR - 20200225 IS - 1756-9966 (Electronic) IS - 0392-9078 (Print) IS - 0392-9078 (Linking) VI - 38 IP - 1 DP - 2019 Feb 12 TI - MiR-223-3p functions as a tumor suppressor in lung squamous cell carcinoma by miR-223-3p-mutant p53 regulatory feedback loop. PG - 74 LID - 10.1186/s13046-019-1079-1 [doi] LID - 74 AB - BACKGROUND: MicroRNAs have an important role in diverse biological processes including tumorigenesis. MiR-223 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in lung squamous cell carcinoma (LSCC). The following study investigates the role of miR-223-3p in LSCC growth and metastasis and its underlying mechanism. METHODS: MicroRNA profiling analyses were conducted to determine differential miRNAs expression levels in LSCC tumor tissues that successfully formed xenografts in immunocompromised mice (XG) and failed tumor tissues (no-XG). RT-PCR and in situ hybridization (ISH) was performed to evaluate the expression of miR-223-3p in 12 paired adjacent normal tissues and LSCC specimens. Cell proliferation and migration were assessed by CCK-8, colony formation and Transwell assay, respectively. The role of miR-223-3p in LSCC tumorigenesis was examined using xenograft nude models. Bioinformatics analysis, Dual-luciferase reporter assays, Chromatin immunoprecipitation (ChIP) assay and Western blot analysis were used to identify the direct target of miR-223-3p and its interactions. RESULTS: MiR-223-3p was downregulated in LSCC tissues that successfully formed xenografts (XG) compared with tumor tissues that failed (no-XG), which was also significantly reduced in LSCC tissues compared with the adjacent normal tissues. Gain- and loss-of function experiments showed that miR-223-3p inhibited proliferation and migration in vitro. More importantly, miR-223-3p overexpression greatly suppressed tumor growth in vivo. Mechanistically, we found that mutant p53 bound to the promoter region of miR-223 and reduced its transcription. Meanwhile, p53 is a direct target of miR-223-3p. Thus, miR-223-3p regulated mutant p53 expression in a feedback loop that inhibited cell proliferation and migration. CONCLUSIONS: Our study identified miR-223-3p, as a tumor suppressor gene, markedly inhibited cell proliferation and migration via miR-223-3p-mutant p53 feedback loop, which suggested miR-223-3p might be a new therapeutic target in LSCC bearing p53 mutations. FAU - Luo, Peng AU - Luo P AD - Department of Clinical Laboratory, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Wang, Qi AU - Wang Q AD - Anhui Medical University, Hefei, China. FAU - Ye, Yuanyuan AU - Ye Y AD - School of Life Sciences, University of Science and Technology of China, Hefei, China. FAU - Zhang, Ju AU - Zhang J AD - Department of Clinical Laboratory, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Lu, Dapeng AU - Lu D AD - Department of Clinical Laboratory, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Cheng, Longqiang AU - Cheng L AD - Anhui Medical University, Hefei, China. FAU - Zhou, Hangcheng AU - Zhou H AD - Department of Pathology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Xie, Mingran AU - Xie M AD - Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Wang, Baolong AU - Wang B AD - Department of Clinical Laboratory, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230001, People's Republic of China. wbl196555@163.com. LA - eng GR - 1604a0802072/Province science and technology in the Anhui offends pass item/ GR - 1708085QH220/Anhui provincial Natural Science Foundation of China/ GR - 81172172/National Natural Science Foundation of China/ PT - Journal Article DEP - 20190212 PL - England TA - J Exp Clin Cancer Res JT - Journal of experimental & clinical cancer research : CR JID - 8308647 RN - 0 (MIRN223 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Tumor Suppressor Protein p53) SB - IM MH - Animals MH - Carcinoma, Squamous Cell/*genetics/metabolism/pathology MH - Cell Line, Tumor MH - Cell Proliferation MH - Genes, Tumor Suppressor/*physiology MH - Humans MH - Lung Neoplasms/*genetics/metabolism/pathology MH - Mice MH - MicroRNAs/*metabolism MH - Tumor Suppressor Protein p53/*metabolism PMC - PMC6373043 OTO - NOTNLM OT - Mutant p53-miR-223-3p-feedback loop-lung squamous cell carcinoma COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of the Institutional Ethical Review Board of Anhui Provincial Hospital. All patients studied signed an informed consent for participation. All animal procedures and care were conducted in accordance with institutional guidelines and in compliance with national and international laws and policies. CONSENT FOR PUBLICATION: Not applicable. 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- 2019/02/14 06:00 MHDA- 2019/06/25 06:00 PMCR- 2019/02/12 CRDT- 2019/02/14 06:00 PHST- 2018/09/12 00:00 [received] PHST- 2019/02/06 00:00 [accepted] PHST- 2019/02/14 06:00 [entrez] PHST- 2019/02/14 06:00 [pubmed] PHST- 2019/06/25 06:00 [medline] PHST- 2019/02/12 00:00 [pmc-release] AID - 10.1186/s13046-019-1079-1 [pii] AID - 1079 [pii] AID - 10.1186/s13046-019-1079-1 [doi] PST - epublish SO - J Exp Clin Cancer Res. 2019 Feb 12;38(1):74. doi: 10.1186/s13046-019-1079-1.