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Long non-coding RNA PROX1-AS1 knockdown upregulates microRNA-519d-3p to promote chemosensitivity of retinoblastoma

Yanyan Chen1, Boyang Lu1, Lei Liu1

  • 1Department of Ophthalmology, The First Hospital of Jilin University, Changchun Jilin, China.

Cell Cycle (Georgetown, Tex.)
|September 29, 2021
PubMed
Abstract

Insights

Long non-coding RNA PROX1-AS1 promotes retinoblastoma drug resistance by sponging miR-519d-3p, which targets SOX2. Inhibiting PROX1-AS1 enhances chemosensitivity in retinoblastoma cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are key regulators in tumor progression.
  • The specific roles of lncRNAs, such as PROX1-antisense RNA1 (PROX1-AS1), in sponging miRNAs like miR-519d-3p within the context of retinoblastoma (RB) remain under-investigated.
  • Understanding these interactions is crucial for developing novel therapeutic strategies against RB.

Purpose of the Study:

  • To elucidate the functional role of the PROX1-AS1/miR-519d-3p/sex determining region Y-box 2 (SOX2) axis in the chemosensitivity of retinoblastoma (RB) cells.
  • To investigate the molecular mechanisms by which PROX1-AS1 influences RB cell drug resistance and malignant behaviors.
  • To determine the regulatory relationship between PROX1-AS1, miR-519d-3p, and SOX2 in RB.

Main Methods:

  • Quantitative analysis of PROX1-AS1, miR-519d-3p, and SOX2 expression in RB tissues and cell lines, including drug-resistant models.
  • In vitro functional assays to assess the impact of PROX1-AS1 or miR-519d-3p manipulation on drug resistance, proliferation, migration, invasion, and apoptosis in RB cells.
  • Molecular experiments to confirm the direct binding interactions between PROX1-AS1 and miR-519d-3p, and between miR-519d-3p and SOX2.

Main Results:

  • PROX1-AS1 and SOX2 were found to be upregulated, while miR-519d-3p was downregulated in RB tissues and particularly in drug-resistant RB cells.
  • Downregulation of PROX1-AS1 or upregulation of miR-519d-3p significantly reduced drug resistance, proliferation, migration, and invasion, while promoting apoptosis in drug-resistant RB cells.
  • Experimental evidence confirmed that PROX1-AS1 acts as a sponge for miR-519d-3p, and miR-519d-3p directly targets SOX2.

Conclusions:

  • PROX1-AS1 knockdown leads to increased miR-519d-3p levels, thereby enhancing the chemosensitivity of retinoblastoma cells through the targeting of SOX2.
  • The PROX1-AS1/miR-519d-3p/SOX2 pathway represents a critical regulatory mechanism influencing retinoblastoma chemosensitivity and progression.
  • Targeting this axis holds therapeutic potential for overcoming drug resistance in retinoblastoma.
Keywords:
Retinoblastomaapoptosislong non-coding rna prox1-antisense rna1microrna-519d-3pproliferationsex determining region y-box 2

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