Hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV/CCN3

Jason R. Dobson, Hanna Taipaleenma¨ki, Yu Jie Hu, Deli Hong, Andre J van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian, Jitesh Pratap

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: For treatment and prevention of metastatic disease, one of the premier challenges is the identification of pathways and proteins to target for clinical intervention. Micro RNAs (miRNAs) are short, non-coding RNAs, which regulate cellular activities by either mRNA degradation or translational inhibition. Our studies focused on the invasive properties of hsa-mir30c based on its high expression in MDA-MB-231 metastatic cells and our bioinformatic analysis of the Cancer Genome Atlas that identified aberrant hsa-mir-30c to be associated with poor survival.Methods: Contributions of hsa-mir-30c to breast cancer cell invasion were examined by Matrigel invasion transwell assays following modulation of hsa-mir-30c or hsa-mir-30c* levels in MDA-MB-231 cells. hsa-mir-30c in silico predicted targets linked to cell invasion were screened for targeting by hsa-mir-30c in metastatic breast cancer cells by RT-qPCR. The contribution to invasion by a target of hsa-mir-30c, Nephroblastoma overexpressed (NOV), was characterized by siRNA and invasion assays. Significant effects were determined using Student's T-tests with Welch's correction for unequal variance.Results: MCF-7 and MDA-MB-231 cells were used as models of poorly invasive and late-stage metastatic disease, respectively. By modulating the levels of hsa-mir-30c in these cells, we observed concomitant changes in breast cancer cell invasiveness. From predicted targets of hsa-mir-30c that were related to cellular migration and invasion, NOV/CCN3 was identified as a novel target of hsa-mir-30c. Depleting NOV by siRNA caused a significant increase in the invasiveness of MDA-MB-231 cells is a regulatory protein associated with the extracellular matrix.Conclusions: NOV/CCN3 expression, which protects cells from invasion, is known in patient tumors to inversely correlate with advanced breast cancer and metastasis. This study has identified a novel target of hsa-mir-30c, NOV, which is an inhibitor of the invasiveness of metastatic breast cancer cells. Thus, hsa-mir-30c-mediated inhibition of NOV levels promotes the invasive phenotype of MDA-MB-231 cells and significantly, the miR-30/NOV pathways is independent of RUNX2, a known target of hsa-mir-30c that promotes osteolytic disease in metastatic breast cancer cells. Our findings allow for mechanistic insight into the clinical observation of poor survival of patients with elevated hsa-mir-30c levels, which can be considered for miRNA-based translational studies.

Original languageEnglish (US)
Article number73
JournalCancer Cell International
Volume14
Issue number1
DOIs
StatePublished - Aug 2 2014

Fingerprint

Wilms Tumor
Breast Neoplasms
Phenotype
MicroRNAs
Small Interfering RNA
Untranslated RNA
Survival
Atlases
RNA Stability
Computational Biology
Computer Simulation
Extracellular Matrix
Neoplasms
Proteins

Keywords

  • Hsa-mir-30c breast cancer
  • Invasion
  • Metastasis
  • miRNA
  • NOV/CCN3

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Genetics

Cite this

Dobson, J. R., Taipaleenma¨ki, H., Hu, Y. J., Hong, D., van Wijnen, A. J., Stein, J. L., ... Pratap, J. (2014). Hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV/CCN3. Cancer Cell International, 14(1), [73]. https://doi.org/10.1186/s12935-014-0073-0

Hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV/CCN3. / Dobson, Jason R.; Taipaleenma¨ki, Hanna; Hu, Yu Jie; Hong, Deli; van Wijnen, Andre J; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.; Pratap, Jitesh.

In: Cancer Cell International, Vol. 14, No. 1, 73, 02.08.2014.

Research output: Contribution to journalArticle

Dobson, JR, Taipaleenma¨ki, H, Hu, YJ, Hong, D, van Wijnen, AJ, Stein, JL, Stein, GS, Lian, JB & Pratap, J 2014, 'Hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV/CCN3', Cancer Cell International, vol. 14, no. 1, 73. https://doi.org/10.1186/s12935-014-0073-0
Dobson, Jason R. ; Taipaleenma¨ki, Hanna ; Hu, Yu Jie ; Hong, Deli ; van Wijnen, Andre J ; Stein, Janet L. ; Stein, Gary S. ; Lian, Jane B. ; Pratap, Jitesh. / Hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV/CCN3. In: Cancer Cell International. 2014 ; Vol. 14, No. 1.
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AU - van Wijnen, Andre J

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KW - Hsa-mir-30c breast cancer

KW - Invasion

KW - Metastasis

KW - miRNA

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