Open Access

Downregulation of microRNA‑1246 inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting thrombospondin‑2

  • Authors:
    • Ping Du
    • Yue‑Hua Lai
    • De‑Sheng Yao
    • Jun‑Ying Chen
    • Nan Ding
  • View Affiliations

  • Published online on: July 5, 2019     https://doi.org/10.3892/ol.2019.10571
  • Pages: 2491-2499
  • Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cervical cancer pathogenesis is regulated by numerous factors, including microRNAs. MicroRNA 1246 (miR‑1246) has been shown to serve a role in cervical cancer tumorigenesis. However, the mechanisms through which miR‑1246 exerts its oncogenic effects are largely unknown. The aim of the current study was to evaluate the effects of lentivirus‑mediated miR‑1246 knockdown on the biological characteristics and behavior of cervical cancer cells, and to identify the downstream signaling pathways affected by miR‑1246 knockdown. Short hairpins inhibiting miR‑1246 were synthesized and cloned into a recombinant lentiviral vector (LV‑miR‑1246‑Inh), which was then used to infect SiHa cervical cancer cells. The effects of LV‑miR‑1246‑Inh infection on cell invasion, proliferation and apoptosis were evaluated by Transwell assay, Cell Counting Kit‑8 assay and flow cytometry, respectively. Thrombospondin‑2 (THBS2), matrix metalloproteinase 2 (MMP2), MMP9 and extracellular matrix (ECM) component expression levels were evaluated, and the growth of xenograft tumors formed following injection of SiHa cells with knockdown of miR‑1246 was assessed. miR‑1246 downregulation in SiHa cells decreased proliferation, induced apoptosis and upregulated THBS2 expression. Furthermore, MMP2 and MMP9 levels were downregulated, whereas components of the ECM were upregulated subsequent to miR‑1246 knockdown, indicating that this miRNA regulates cervical cancer cell pathogenesis via the THBS2/MMP/ECM pathway. Notably, SiHa cells with miR‑1246 downregulation had a markedly decreased ability to form tumors in vivo. These results suggest that miR‑1246 functions during cervical cancer pathogenesis and tumor formation via the THBS2/MMP/ECM signaling pathway. These findings support the future use of miR‑1246 suppression in the treatment of cervical cancer.

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September 2019
Volume 18 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Du, P., Lai, Y., Yao, D., Chen, J., & Ding, N. (2019). Downregulation of microRNA‑1246 inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting thrombospondin‑2. Oncology Letters, 18, 2491-2499. https://doi.org/10.3892/ol.2019.10571
MLA
Du, P., Lai, Y., Yao, D., Chen, J., Ding, N."Downregulation of microRNA‑1246 inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting thrombospondin‑2". Oncology Letters 18.3 (2019): 2491-2499.
Chicago
Du, P., Lai, Y., Yao, D., Chen, J., Ding, N."Downregulation of microRNA‑1246 inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting thrombospondin‑2". Oncology Letters 18, no. 3 (2019): 2491-2499. https://doi.org/10.3892/ol.2019.10571