Tumor Biology

, Volume 35, Issue 10, pp 10011–10017 | Cite as

Downregulation of tumor suppressor menin by miR-421 promotes proliferation and migration of neuroblastoma

  • Yu Li
  • Wei Li
  • Jian-Guo Zhang
  • Hai-Yang Li
  • Yong-Ming Li
Research Article
First Online:
Received:
Accepted:

Abstract

Neuroblastoma, featured by a high rate of spontaneous remissions, is the most common extra-cranial solid tumor in infants and children. Numerous reports have demonstrated that MicroRNAs (miRNAs) play essential roles in cancer progression, including cell proliferation, apoptosis, invasion, metastasis and angiogenesis. miR-421 functions as an onco-miR in some malignancies. However, its role in neuroblastoma remains poorly understood. In the present study, we found that miR-421 was increased in neuroblastoma tissues compared with matched adjacent normal tissues. Forced overexpression of miR-421 substantially enhanced cell proliferation, cell-cycle progression, migration, and invasion of neuroblastoma cells. At the molecular level, tumor suppressor menin was found to be a target of miR-421. Furthermore, downregulation of menin by small interfering RNA oligos exhibited similar effects with overexpression of miR-421. On the other hand, overexpression of menin partially reversed the proliferative effects of miR-421 in neuroblastoma cells. Collectively, miR-421 may promote neuroblastoma cell growth and motility partially by targeting menin.

Keywords

MiR-421 Neuroblastoma Menin Tumor suppressor 
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Notes

Conflicts of interest

None.

Supplementary material

13277_2014_1921_Fig7_ESM.gif (7 kb)
Supplementary Figure 1

Expression levels of miR-421 were compared in SHSY5Y and SHEP cells by real-time PCR. (A)Expression of miR-421 was determined in SHEP cells after transfection of miR-421 mimics or negative controls (NC). (C) The cell viability of SHEP cells was determined by MTT assays. (D) The growth curve of SHEP cells after miR-421 transfection compared to NC. (E) The cell proliferative potential (BrdU) was determined in SHEP cells. A450 absorption was assayed after transfection for 24 hr. (F) The cell-cycle phase of SHSY5Y cells were analyzed by flow cytometry. *p < 0.05, ** p < 0.01, *** p < 0.001, compared with NC. (GIF 6 kb)

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High resolution image (TIFF 1045 kb)
13277_2014_1921_Fig8_ESM.gif (6 kb)
Supplementary Figure 2

(A) Expression levels of miR-421 were determined in three cell lines by real-time PCR. (B)Expression of miR-421 was determined in IMR-32 cells after transfection of miR-421 mimics or negative controls (NC). (C) The cell viability of IMR-32 cells was determined by MTT assays. (D) The growth curve of IMR-32 cells after miR-421 transfection compared to NC. (E) The cell proliferative potential (BrdU) was determined in IMR-32cells. A450 absorption was assayed after transfection for 24 hr. (F) The cell-cycle phase of IMR-32 cells was analyzed by flow cytometry. *p < 0.05, ** p < 0.01, *** p < 0.001, compared with NC. (GIF 6 kb)

13277_2014_1921_MOESM2_ESM.tif (995 kb)
High resolution image (TIFF 995 kb)
13277_2014_1921_Fig9_ESM.gif (1 kb)
Supplementary Figure 3

Representative Menin protein levels in human NB and adjacent normal tissues from two patients. 40 μg amount of tissue lysates were used in the western blot experiments. (GIF 0 kb)

13277_2014_1921_MOESM3_ESM.tif (150 kb)
High resolution image (TIFF 150 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yu Li
    • 1
  • Wei Li
    • 2
  • Jian-Guo Zhang
    • 1
  • Hai-Yang Li
    • 1
  • Yong-Ming Li
    • 1
  1. 1.Department of Neurosurgery, Henan Provincial People’s HospitalZhengzhou UniversityHenanChina
  2. 2.Department of Neurology, Henan Provincial People’s HospitalZhengzhou UniversityHenanChina

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