Silencing the double-stranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion

Yuqi Guo, Peng Tian, Chuan Yang, Zhibing Liang, Min Li, Michelle Sims, Lu Lu, Zhan Zhang, Hongwei Li, Lawrence Pfeffer, Junming Yue

Research output: Contribution to journalArticle

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Abstract

Purpose: To evaluate the role of DiGeorge Critical Region 8 (DGCR8), a key component of miRNA biogenesis pathway in ovarian cancer. Methods: The expression of DGCR8 in ovarian cancer was detected by immunostaining and DGCR8 knockdown in ovarian cancer cells was achieved using lentiviral shRNA. Differential expression of miRNAs was determined using Nanostring miRNA arrays and validated by real-time RT-PCR. Results: DGCR8 was highly expressed in ovarian cancer. Knockdown of DGCR8 expression inhibits cell proliferation, migration, and invasion, as well as sensitizes cells to apoptosis induced by the chemotherapeutic drug cisplatin. Cellular survival pathways including ERK1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT were attenuated in DGCR8 knockdown cells. DGCR8 knockdown results in dysregulated miRNA gene expression. miR-27b was identified as the most highly down-regulated miRNA in DGCR8 knockdown cells and promoted cell proliferation in ovarian cancer cells. Conclusions: DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b.

Original languageEnglish (US)
Pages (from-to)769-778
Number of pages10
JournalPharmaceutical Research
Volume32
Issue number3
DOIs
StatePublished - Jan 1 2015

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RNA-Binding Proteins
Cell proliferation
MicroRNAs
Ovarian Neoplasms
Cell Movement
Cell Proliferation
Cells
Phosphatidylinositol 3-Kinase
Mitogen-Activated Protein Kinase 1
Gene expression
Small Interfering RNA
Cisplatin
Oncogenes
Real-Time Polymerase Chain Reaction
Apoptosis
Gene Expression
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Silencing the double-stranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion. / Guo, Yuqi; Tian, Peng; Yang, Chuan; Liang, Zhibing; Li, Min; Sims, Michelle; Lu, Lu; Zhang, Zhan; Li, Hongwei; Pfeffer, Lawrence; Yue, Junming.

In: Pharmaceutical Research, Vol. 32, No. 3, 01.01.2015, p. 769-778.

Research output: Contribution to journalArticle

Guo, Yuqi ; Tian, Peng ; Yang, Chuan ; Liang, Zhibing ; Li, Min ; Sims, Michelle ; Lu, Lu ; Zhang, Zhan ; Li, Hongwei ; Pfeffer, Lawrence ; Yue, Junming. / Silencing the double-stranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion. In: Pharmaceutical Research. 2015 ; Vol. 32, No. 3. pp. 769-778.
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AU - Tian, Peng

AU - Yang, Chuan

AU - Liang, Zhibing

AU - Li, Min

AU - Sims, Michelle

AU - Lu, Lu

AU - Zhang, Zhan

AU - Li, Hongwei

AU - Pfeffer, Lawrence

AU - Yue, Junming

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N2 - Purpose: To evaluate the role of DiGeorge Critical Region 8 (DGCR8), a key component of miRNA biogenesis pathway in ovarian cancer. Methods: The expression of DGCR8 in ovarian cancer was detected by immunostaining and DGCR8 knockdown in ovarian cancer cells was achieved using lentiviral shRNA. Differential expression of miRNAs was determined using Nanostring miRNA arrays and validated by real-time RT-PCR. Results: DGCR8 was highly expressed in ovarian cancer. Knockdown of DGCR8 expression inhibits cell proliferation, migration, and invasion, as well as sensitizes cells to apoptosis induced by the chemotherapeutic drug cisplatin. Cellular survival pathways including ERK1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT were attenuated in DGCR8 knockdown cells. DGCR8 knockdown results in dysregulated miRNA gene expression. miR-27b was identified as the most highly down-regulated miRNA in DGCR8 knockdown cells and promoted cell proliferation in ovarian cancer cells. Conclusions: DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b.

AB - Purpose: To evaluate the role of DiGeorge Critical Region 8 (DGCR8), a key component of miRNA biogenesis pathway in ovarian cancer. Methods: The expression of DGCR8 in ovarian cancer was detected by immunostaining and DGCR8 knockdown in ovarian cancer cells was achieved using lentiviral shRNA. Differential expression of miRNAs was determined using Nanostring miRNA arrays and validated by real-time RT-PCR. Results: DGCR8 was highly expressed in ovarian cancer. Knockdown of DGCR8 expression inhibits cell proliferation, migration, and invasion, as well as sensitizes cells to apoptosis induced by the chemotherapeutic drug cisplatin. Cellular survival pathways including ERK1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT were attenuated in DGCR8 knockdown cells. DGCR8 knockdown results in dysregulated miRNA gene expression. miR-27b was identified as the most highly down-regulated miRNA in DGCR8 knockdown cells and promoted cell proliferation in ovarian cancer cells. Conclusions: DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b.

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