Long non‑coding RNA MLK7‑AS1 promotes proliferation in human colorectal cancer via downregulation of p21 expression

Mol Med Rep. 2019 Feb;19(2):1210-1221. doi: 10.3892/mmr.2018.9702. Epub 2018 Nov 28.

Abstract

Current studies have highlighted long non‑coding RNAs (lncRNAs) as critical regulators in various cancers, including colorectal cancer (CRC). By utilizing publicly available data from The Cancer Genome Atlas dataset, MLK7 antisense RNA 1 (MLK7‑AS1) was identified as a novel lncRNA that correlated with CRC progression. The results of reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) revealed a significant upregulation of MLK7‑AS1 in both CRC tissue samples and cell lines. In addition, a positive correlation was observed between increased MLK7‑AS1 expression and several clinicopathological factors in patients with CRC. Importantly, MLK7‑AS1 knockdown suppressed CRC cell proliferation and promoted G1/G0 phase arrest and apoptosis in vitro, whereas MLK7‑AS1 overexpression exhibited opposite effects. Consistently, decreased MLK7‑AS1 expression inhibited tumor growth in vivo. Furthermore, RT‑qPCR and western blot assays revealed that p21 may be a potential downstream target of MLK7‑AS1. To the best of the authors' knowledge, this is the first study to report that MLK7‑AS1 has potential as a biomarker and may promote proliferation in CRC partially through downregulating p21 expression.

Keywords: long non-coding RNA; MLK7-AS1; colorectal cancer; proliferation; P21.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • HCT116 Cells
  • Humans
  • MAP Kinase Kinase Kinases
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Muscle Proteins / genetics*
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Antisense / genetics
  • RNA, Long Noncoding / genetics*
  • Up-Regulation / genetics

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Muscle Proteins
  • RNA, Antisense
  • RNA, Long Noncoding
  • Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases
  • MAP3K20 protein, human