SOX2 inhibits LLGL2 polarity protein in esophageal squamous cell carcinoma via miRNA-142-3p

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis.
• The epithelial-to-mesenchymal transition (EMT) is a key process in cancer progression and metastasis.
• The role of lethal (2) giant larvae protein homolog 2 (LLGL2) in ESCC remains largely unexplored.

Purpose of the Study:

• To investigate the function of LLGL2 in ESCC progression.
• To elucidate the underlying molecular mechanisms, including its role in EMT.
• To assess the potential of LLGL2 as a therapeutic target in esophageal cancer.

Main Methods:

• LLGL2 expression analysis in ESCC tissues and cell lines.
• LLGL2 knockdown and overexpression experiments in ESCC cells.
• Assessment of cell proliferation, migration, and invasion using CCK-8 and Transwell assays.
• Analysis of EMT markers (E-cadherin, N-cadherin, Vimentin) via Western blotting.
• Chromatin Immunoprecipitation (Chip) assays to investigate SOX2 binding.
• MicroRNA (miRNA) profiling and validation using quantitative real-time PCR.
• Parallel reaction monitoring-Mass spectrometry (PRM-MS) for protein quantification.

Main Results:

• LLGL2 was significantly upregulated in ESCC tissues and correlated with poor patient survival.
• LLGL2 overexpression promoted ESCC cell proliferation, migration, and invasion, while LLGL2 knockdown inhibited these processes.
• LLGL2 facilitated EMT by upregulating mesenchymal markers and downregulating epithelial markers.
• LLGL2 directly bound to the promoter region of SOX2, increasing its transcription.
• LLGL2 influenced the expression of specific miRNAs involved in EMT regulation.
• LLGL2 knockdown suppressed tumor growth and metastasis in vivo.

Conclusions:

• LLGL2 plays a critical oncogenic role in ESCC by promoting proliferation, migration, invasion, and EMT.
• LLGL2 acts, at least in part, by regulating SOX2 expression and specific miRNA profiles.
• LLGL2 represents a promising therapeutic target for esophageal cancer treatment.