The Down-Regulation of Circ_0059707 in Acute Myeloid Leukemia Promotes Cell Growth and Inhibits Apoptosis by Regulating miR-1287-5p

Curr Oncol. 2022 Sep 18;29(9):6688-6699. doi: 10.3390/curroncol29090525.

Abstract

Acute myeloid leukemia (AML) is the most common type of hematological malignancy. Recently, an increasing number of reports have shown that many circular RNAs can act as effective targets for AML. However, the roles of circ_0059707 in AML remain largely unclear. In this study, we found that the expression levels of circ_0059707 were significantly decreased in AML patients with respect to normal controls (p < 0.001). Low expression levels of circ_0059707 were also associated with a poor prognosis. Furthermore, circ_0059707 overexpression inhibited cell growth and promoted apoptosis in leukemia cells, compared with control cells. Circ_0059707- and empty plasmid-transfected cells were injected subcutaneously into BALB/c nude mice. We found that the tumor volume was significantly lower in mice in the circ_0059707 group than in control mice (p < 0.01). Nuclear pyknosis, nuclear fragmentation, nuclear dissolution, and cell necrosis were observed in the circ_0059707 group by HE staining. CircInteractome analysis showed that 25 microRNAs (miRNAs), including miR-1287-5p, ©-miR-1825, a©hsa-miR-326, may be potential targets for circ_0059707. The expression of these miRNAs was analyzed in both the GEO GSE51908 and the GSE142700 databases. miR-1287-5p expression was lower in AML patients compared with controls in both the GSE51908 and the GSE142700 datasets. Moreover, we demonstrated that miR-1287-5p expression was down-regulated in AML patients and up-regulated in circ_0059707-overexpressing cells. Collectively, our research demonstrated that the down-regulation of circ_0059707 was highly evident in de novo AML patients. Our analysis also demonstrated that circ_0059707 inhibited cell growth and promoted apoptosis by up-regulating miR-1287-5p.

Keywords: acute myeloid leukemia; circ_0059707; circular RNA; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Down-Regulation
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • RNA, Circular* / genetics

Substances

  • MIRN1287 microRNA, human
  • MIRN326 microRNA, human
  • MicroRNAs
  • RNA, Circular

Grants and funding

This study was supported by the National Natural Science foundation of China (81900163, 81970118), “Liu Ge Yi Gong Cheng” of Jiangsu Province (LGY2018024), China Postdoctoral Science Foundation project (2016M601748), youth medical talents project of “Ke Jiao Qiang Wei” of Jiangsu province (QNRC2016450), Zhenjiang Clinical Research Center of Hematology (SS2018009), Social Development Foundation of Zhenjiang (SH2019065, SH2019067), Scientific Research Project of the Fifth 169 Project of Zhenjiang (21), Project of Zhenjiang First People’s Hospital (Y2021010-S).