High expression of long intergenic non-coding RNA LINC00662 contributes to malignant growth of acute myeloid leukemia cells by upregulating ROCK1 via sponging microRNA-340-5p

Eur J Pharmacol. 2019 Sep 15;859:172535. doi: 10.1016/j.ejphar.2019.172535. Epub 2019 Jul 12.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as crucial regulatory factors in diverse pathological processes, especially in tumorigenesis. Accumulating evidence has demonstrated that long intergenic non-coding RNA 00662 (LINC00662) is overexpressed in multiple cancers and facilitates cancer development and progression. However, whether LINC00662 is involved in acute myeloid leukemia (AML) remains unknown. This study was aimed to explore the expression, biological function and regulatory mechanism of LINC00662 in AML. Here, we found that LINC00662 was significantly increased in AML tissues and cell lines. Knockdown of LINC00662 significantly reduced the growth of AML cells and upregulated AML cell apoptosis. In contrast, overexpression of LINC00662 promoted AML cell growth. MicroRNA-340-5p (miR-340-5p) was predicted as a target of LINC00662. Luciferase reporter assays and RNA pull-down assays confirmed that LINC00662 directly interacted with miR-340-5p. Expression of miR-340-5p was downregulated in AML and silencing of LINC00662 upregulated miR-340-5p expression in AML cells. Moreover, overexpression of miR-340-5p inhibited cell growth and increased apoptosis in AML cells. Inhibition of miR-340-5p significantly reversed the inhibitory effect of LINC00662 silencing on AML cell growth. In addition, Rho-associated protein kinase 1 (ROCK1) was verified as a target gene of miR-340-5p in AML cells. Restoration of ROCK1 expression partially reversed LINC00662 silencing or miR-340-5p overexpression-mediated inhibitory effect on AML cell growth. Overall, our results demonstrate that LINC00662 contributes to the malignant growth of AML cells by upregulating ROCK1 via sponging miR-340-5p, highlighting the important role of the LINC00662/miR-340-5p/ROCK1 axis in regulating the malignant behavior of AML cells.

Keywords: Acute myeloid leukemia; LINC00662; ROCK1; miR-340-5p.

MeSH terms

  • Apoptosis / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology*
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Up-Regulation / genetics*
  • rho-Associated Kinases / metabolism*

Substances

  • MIRN340 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • ROCK1 protein, human
  • rho-Associated Kinases