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Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma

Huidi Liu1,2,3,4,5, Zheng Zeng1,2,3, Mitra Afsharpad6

  • 1Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China.

Frontiers in Oncology
|February 22, 2020
PubMed

Insights

Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) promotes ovarian clear cell carcinoma (OCCC) progression. Targeting IGF2BP3 inhibits OCCC cell proliferation, migration, invasion, and tumor growth, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ovarian Clear Cell Carcinoma (OCCC) has a poor prognosis due to limited effective therapies.
  • Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is an RNA-binding protein influencing gene expression post-transcriptionally.

Purpose of the Study:

  • To investigate the role of IGF2BP3 in OCCC progression.
  • To determine the association between IGF2BP3 expression and clinicopathological parameters in OCCC.
  • To evaluate IGF2BP3 as a potential therapeutic target for OCCC.

Main Methods:

  • Analysis of 328 OCCC samples from the AOVT and COEUR cohorts.
  • Assessment of IGF2BP3 expression and its correlation with clinicopathological parameters and survival.
  • In vitro and in vivo knockdown experiments using IGF2BP3-overexpressing OCCC cell lines (ES2, OVMANA) with siRNAs.
  • Evaluation of cell proliferation, viability, migration, invasion, and apoptosis.
  • Measurement of metastasis-related proteins MMP2 and MMP9.

Main Results:

  • Positive IGF2BP3 expression was more frequent in Stage III OCCC and associated with unfavorable overall survival.
  • IGF2BP3 mRNA expression was significantly increased in OCCC cell lines compared to normal ovarian surface epithelium.
  • IGF2BP3 knockdown inhibited OCCC cell proliferation, viability, migration, and invasion, and enhanced apoptosis.
  • In vivo tumor growth was significantly reduced following IGF2BP3 siRNA treatment.
  • Down-regulation of MMP2 and MMP9 proteins was observed after IGF2BP3 knockdown.

Conclusions:

  • IGF2BP3 expression is a potential prognostic biomarker for OCCC.
  • IGF2BP3 plays a significant role in OCCC progression by affecting key cellular functions.
  • IGF2BP3 represents a potential therapeutic target for OCCC intervention strategies.
Keywords:
IGF2BP3IMP3MMPsclear cell carcinomametastasisovarian cancerprognosis

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