Related Experiment Video
Updated: May 23, 2025
Reconstruct Human Retinoblastoma In Vitro
Published on: October 11, 2022
SOX4 as a Key Oncogene Driving Tumor Invasion in Retinoblastoma
Jiahe Nie1, Junjie Tang1, Zhihui Zhang1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Purpose:
This study aims to explore the role of SRY-related HMG box transcription factor 4 (SOX4) in promoting invasion in retinoblastoma (RB) and to elucidate the underlying oncogenic pathways.
Methods:
SOX4 expression in human retina, intraocular RB, and extraocular RB samples was evaluated using bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq), with further evaluation in RB cell lines (Y79, WERI-RB1). Small interfering RNA-mediated knockdown was performed in RB cell lines, followed by functional assays including CCK-8, EdU, colony formation, and transwell assays. An orthotopic xenograft model with SOX4 knockdown was utilized to assess tumor invasion. RNA-seq was performed on SOX4 knockdown (si-SOX4) and control (si-NC) Y79 cells to explore downstream signaling pathways.
Results:
RNA-seq and scRNA-seq data revealed that SOX4, E2F3, and DEK were significantly upregulated in RB tissues compared to normal retina. Notably, SOX4 expression was particularly elevated in extraocular RB tissues, especially in MKI67+ photoreceptorness-decreased cells. Knockdown of SOX4 in RB cell lines caused decreased proliferation, colony formation, migration, and reversal of epithelial-to-mesenchymal transition markers (N-cadherin, E-cadherin, vimentin). In vivo, SOX4 knockdown resulted in fewer cases of anterior chamber involvement and eyeball wall invasion in an orthotopic xenograft model. RNA-seq analysis revealed that SOX4 knockdown altered the Wnt/β-catenin and cyclin D1 signaling pathways.
Conclusions:
SOX4 plays a critical role in driving local invasion in RB, and targeting SOX4 may provide new insights into the molecular mechanisms of RB invasion, potentially leading to improved therapeutic strategies for RB treatment.
Insights
SRY-related HMG box transcription factor 4 (SOX4) promotes retinoblastoma (RB) invasion by altering Wnt/β-catenin and cyclin D1 pathways. Targeting SOX4 may offer new therapeutic strategies for RB treatment.
Area of Science:
- Ophthalmology
- Molecular Biology
- Oncology
Background:
- Retinoblastoma (RB) is a pediatric eye cancer.
- Understanding the molecular mechanisms driving RB invasion is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of SRY-related HMG box transcription factor 4 (SOX4) in promoting retinoblastoma (RB) invasion.
- To elucidate the underlying oncogenic pathways involved in SOX4-mediated RB invasion.
Main Methods:
- SOX4 expression was analyzed in RB tissues and cell lines using bulk and single-cell RNA sequencing (RNA-seq, scRNA-seq).
- SOX4 was knocked down in RB cell lines (Y79, WERI-RB1) to assess functional changes via CCK-8, EdU, colony formation, and transwell assays.
- An orthotopic xenograft model was used to evaluate the in vivo effects of SOX4 knockdown on tumor invasion. Downstream pathways were analyzed by RNA-seq.
Main Results:
- SOX4, E2F3, and DEK were upregulated in RB tissues, with SOX4 elevated in extraocular RB, particularly in MKI67+ cells.
- SOX4 knockdown reduced RB cell proliferation, colony formation, and migration, and reversed epithelial-to-mesenchymal transition markers.
- In vivo, SOX4 knockdown decreased tumor invasion. RNA-seq identified alterations in Wnt/β-catenin and cyclin D1 signaling pathways.
Conclusions:
- SOX4 is a critical driver of local invasion in retinoblastoma.
- Targeting SOX4 presents a potential therapeutic strategy for RB by inhibiting invasion.
- Further research into SOX4's role may uncover novel molecular mechanisms for improved RB treatment.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:33Pleiotropy
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...