<i>MicroRNA-140</i> mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6

DOI DOI IR Web Site 6 Citations 52 References

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  • MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6
  • MicroRNA‐140 mediates RB tumor suppressor function to control stem cell‐like activity through interleukin‐6

Abstract

We established an in vitro cell culture system to determine novel activities of the retinoblastoma (Rb) protein during tumor progression. Rb depletion in p53-null mouse-derived soft tissue sarcoma cells induced a spherogenic phenotype. Cells retrieved from Rb-depleted spheres exhibited slower proliferation and less efficient BrdU incorporation, however, much higher spherogenic activity and aggressive behavior. We discovered six miRNAs, including mmu-miR-18a, -25, -29b, -140, -337, and -1839, whose expression levels correlated tightly with the Rb status and spherogenic activity. Among these, mmu-miR-140 appeared to be positively controlled by Rb and to antagonize the effect of Rb depletion on spherogenesis and tumorigenesis. Furthermore, among genes potentially targeted by mmu-miR-140, Il-6 was upregulated by Rb depletion and downregulated by mmu-mir-140 overexpression. Altogether, we demonstrate the possibility that mmu-mir-140 mediates the Rb function to downregulate Il-6 by targeting its 3'-untranslated region. Finally, we detected the same relationship among RB, hsa-miR-140 and IL-6 in a human breast cancer cell line MCF-7. Because IL-6 is a critical modulator of malignant features of cancer cells and the RB pathway is impaired in the majority of cancers, hsa-miR-140 might be a promising therapeutic tool that disrupts linkage between tumor suppressor inactivation and pro-inflammatory cytokine response.

Supplementary Table1 and Supplementary Table2: We offer the table data with an Excel file

Journal

  • Oncotarget

    Oncotarget 8 (8), 13872-13885, 2017-01-01

    Impact Journals LLC

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