Effect of CXCR4 silencing with shRNA on MAPK signaling in ovarian cancer

Xiuli Wang1, Hongying Wang1, Xia Wei1

  • 1Department of Obstetrics and Gynecology, Liaocheng People's Hospital of Shandong Province, Liaocheng, Shandong 252000, P.R. China.

Oncology Letters
|May 29, 2018
PubMed

Insights

Silencing C-X-C chemokine receptor type 4 (CXCR4) with shRNA inhibits ovarian cancer cell growth. This CXCR4 gene silencing impacts mitogen-activated protein kinase (MAPK) signaling, promoting apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Previous research showed short hairpin RNA (shRNA) targeting of C-X-C chemokine receptor type 4 (CXCR4) inhibits cancer cell proliferation, metastasis, and invasion.
  • CXCR4 is implicated in various cancer progression mechanisms.

Purpose of the Study:

  • To investigate the effects of shRNA-mediated CXCR4 silencing on mitogen-activated protein kinase (MAPK) signaling pathways in human SW626 ovarian cancer cells.
  • To understand the molecular mechanisms underlying CXCR4's role in ovarian cancer.

Main Methods:

  • SW626 ovarian cancer cells were transfected with shRNA targeting CXCR4.
  • Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure apoptosis signal-regulating kinase 1 (ASK1) mRNA expression.
  • Immunocytochemistry and western blotting were employed to assess extracellular-signal-regulated kinase (ERK)1/2 and phosphorylated (p)-c-Jun protein levels.

Main Results:

  • shRNA-CXCR4 silencing led to a significant increase in ASK1 mRNA expression (P<0.05).
  • A significant increase in p-c-Jun protein expression (P<0.05) and a significant decrease in ERK1/2 protein expression (P<0.05) were observed.
  • CXCR4 gene silencing significantly inhibited cell proliferation and promoted cell apoptosis.

Conclusions:

  • shRNA-mediated silencing of CXCR4 in SW626 ovarian cancer cells impacts MAPK signaling.
  • The observed inhibition of cell proliferation and promotion of apoptosis by CXCR4 silencing may be mediated through the MAPK signaling pathway.

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