Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge

J Exp Clin Cancer Res. 2020 Jul 20;39(1):139. doi: 10.1186/s13046-020-01633-8.


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.

Keywords: CRC; Let-7f-1-3p; MK5; MK5-AS1; SNAI1.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Antisense / genetics*
  • RNA, Long Noncoding / genetics*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • RBM4 protein, human
  • RNA, Antisense
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • mirnlet7 microRNA, human
  • MAP-kinase-activated kinase 5
  • Protein Serine-Threonine Kinases