DICP OpenIR
MiR-223-3p functions as a tumor suppressor in lung squamous cell carcinoma by miR-223-3p-mutant p53 regulatory feedback loop
Luo, Peng1; Wang, Qi2; Ye, Yuanyuan3; Zhang, Ju1; Lu, Dapeng1; Cheng, Longqiang2; Zhou, Hangcheng4; Xie, Mingran5; Wang, Baolong6
Corresponding AuthorWang, Baolong(wbl196555@163.com)
KeywordMutant p53-miR-223-3p-feedback loop-lung squamous cell carcinoma
Source PublicationJOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
2019-02-12
ISSN1756-9966
DOI10.1186/s13046-019-1079-1
Volume38Pages:12
Funding ProjectProvince science and technology in the Anhui offends pass item[1604a0802072] ; Anhui provincial Natural Science Foundation of China[1708085QH220] ; National Natural Science Foundation of China[81172172]
Funding OrganizationProvince science and technology in the Anhui offends pass item ; Province science and technology in the Anhui offends pass item ; Anhui provincial Natural Science Foundation of China ; Anhui provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Province science and technology in the Anhui offends pass item ; Province science and technology in the Anhui offends pass item ; Anhui provincial Natural Science Foundation of China ; Anhui provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Province science and technology in the Anhui offends pass item ; Province science and technology in the Anhui offends pass item ; Anhui provincial Natural Science Foundation of China ; Anhui provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Province science and technology in the Anhui offends pass item ; Province science and technology in the Anhui offends pass item ; Anhui provincial Natural Science Foundation of China ; Anhui provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS SubjectOncology
WOS Research AreaOncology
WOS KeywordGAIN-OF-FUNCTION ; MUTANT P53 ; CANCER ; XENOGRAFTS ; EXPRESSION ; DIAGNOSIS ; GENES ; AXIS
AbstractBackground: 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.
Language英语
Funding OrganizationProvince science and technology in the Anhui offends pass item ; Province science and technology in the Anhui offends pass item ; Anhui provincial Natural Science Foundation of China ; Anhui provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Province science and technology in the Anhui offends pass item ; Province science and technology in the Anhui offends pass item ; Anhui provincial Natural Science Foundation of China ; Anhui provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Province science and technology in the Anhui offends pass item ; Province science and technology in the Anhui offends pass item ; Anhui provincial Natural Science Foundation of China ; Anhui provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Province science and technology in the Anhui offends pass item ; Province science and technology in the Anhui offends pass item ; Anhui provincial Natural Science Foundation of China ; Anhui provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS IDWOS:000458776500003
PublisherBMC
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/165951
Collection中国科学院大连化学物理研究所
Corresponding AuthorWang, Baolong
Affiliation1.Univ Sci & Technol China, Affiliated Hosp 1, Dept Clin Lab, Hefei, Anhui, Peoples R China
2.Anhui Med Univ, Hefei, Anhui, Peoples R China
3.Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China
4.Univ Sci & Technol China, Affiliated Hosp 1, Dept Pathol, Hefei, Anhui, Peoples R China
5.Univ Sci & Technol China, Affiliated Hosp 1, Dept Thorac Surg, Hefei, Anhui, Peoples R China
6.Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Clin Lab, Div Life Sci & Med, Hefei 230001, Anhui, Peoples R China
Recommended Citation
GB/T 7714
Luo, Peng,Wang, Qi,Ye, Yuanyuan,et al. MiR-223-3p functions as a tumor suppressor in lung squamous cell carcinoma by miR-223-3p-mutant p53 regulatory feedback loop[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2019,38:12.
APA Luo, Peng.,Wang, Qi.,Ye, Yuanyuan.,Zhang, Ju.,Lu, Dapeng.,...&Wang, Baolong.(2019).MiR-223-3p functions as a tumor suppressor in lung squamous cell carcinoma by miR-223-3p-mutant p53 regulatory feedback loop.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,38,12.
MLA Luo, Peng,et al."MiR-223-3p functions as a tumor suppressor in lung squamous cell carcinoma by miR-223-3p-mutant p53 regulatory feedback loop".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 38(2019):12.
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