Journal
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Volume 39, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13046-020-01633-8
Keywords
MK5-AS1; MK5; Let-7f-1-3p; SNAI1; CRC
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Funding
- National Natural Science Foundation of China [81572349, 81872080]
- Jiangsu Provincial Medical Talent [ZDRCA2016055]
- Science and Technology Department of Jiangsu Province [BK20181148]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- National Natural Science Foundation of Jiangsu [BK20191154]
- Six Talent Peaks Project in Jiangsu Province [WSW-050]
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Background Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown. Methods In this study, quantitative real-time PCR (qPCR) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS1, let-7f-1-3p and MK5 in CRC cells were explored using Cell Counting Kit-8 (CCK8), colony formation and transwell assays. The potential mechanisms of MK5-AS1 were evaluated by RNA pull-down, RNA immunoprecipitation (RIP), dual luciferase reporter assay, chromatin immunoprecipitation (ChIP) and bioinformatics analysis. The effects of MK5-AS1 and MK5 on CRC were investigated by a xenotransplantation model. Results We confirmed that MK5-AS1 was significantly increased in CRC tissues. Knockdown of MK5-AS1 suppressed cell migration and invasion in vitro and inhibited lung metastasis in mice. Mechanistically, MK5-AS1 regulated SNAI1 expression by sponging let-7f-1-3p andcis-regulated the adjacent gene MK5. Moreover, MK5-AS1 recruited RBM4 and eIF4A1 to promote the translation of MK5. Our study verified that MK5 promoted the phosphorylation of c-Jun, which activated the transcription of SNAI1 by directly binding to its promoter. Conclusions MK5-AS1cis-regulated the nearby gene MK5 and acted as a let-7f-1-3p sponge, playing a vital role in CRC tumorigenesis. This study could provide novel insights into molecular therapeutic targets of CRC.
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