Abstract:
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 and cis-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-AS1 cis-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.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Yang T,Chen WC,Shi PC,Liu MR,Jiang T,Song H,Wang JQ,Fan RZ,Pei DS,Song Jdoi
10.1186/s13046-020-01633-8subject
Has Abstractpub_date
2020-07-20 00:00:00pages
139issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-020-01633-8journal_volume
39pub_type
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0821-4
更新日期:2018-07-16 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1030-5
更新日期:2019-01-17 00:00:00
abstract:BACKGROUND:Kidney Renal Clear Cell Carcinoma (KIRC) accounts for 75% of all renal cancers. Previous study had conflict evidences regarding NR1B2 role in cancer, and its expression and biological role in KIRC remained unclear. Our aims were to characterize the role of NR1B2 in KIRC. METHODS:NR1B2 expression in TCGA dat...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1344-3
更新日期:2019-08-07 00:00:00