SOX2 inhibits LLGL2 polarity protein in esophageal squamous cell carcinoma via miRNA-142-3p
Open Access
- 22 September 2022
- journal article
- research article
- Published by Taylor & Francis Ltd in Cancer Biology & Therapy
- Vol. 23 (1), 1-15
- https://doi.org/10.1080/15384047.2022.2126248
Abstract
Elevated SOX2 protein levels correspond to the poor prognosis of patients with esophageal squamous cell carcinoma (ESCC). Poor prognosis is closely correlated with the loss or disruption of cellular polarity; however, the relationships between SOX2 protein and polarity proteins in ESCC remain elusive. Herein, we found that the knockdown of SOX2 significantly decreased miR-142-3p expression and can regulate the translation of LLGL2 protein, a member of the Scribble complex. LLGL2 protein levels in ESCC are negatively correlated with miR-142-3p and SOX2 levels. Moreover, LLGL2 protein expression increased upon SOX2 knockdown in ESCC cell lines, and mutating the binding site for this miRNA in the LLGL2 3’-UTR disrupted its ability to inhibit LLGL2 expression. When LLGL2 was overexpressed, ESCC cell proliferation and invasion were inhibited in vitro and in vivo, which could be elucidated based on changes in gene expression after RNA sequencing, targeted proteomic analysis and bioinformatic assays. However, SOX2 protein did not directly bind to the promoter of miR-142-3p after ChIP sequencing. Together, these findings indicate that a SOX2 regulatory axis governs ESCC proliferation, migration, invasiveness, and apoptosis, thereby providing a potential avenue for future therapeutic intervention.Keywords
Funding Information
- National Natural Science Foundation of China
- Natural Science Foundation of Fujian Province (2021D034)
- the Program from Xiang’an Hospital (PM202012220001)
- the National High Technology Research and Development Program of China (2014AA020541)
- the Program for the Top Young Innovative Talents of Fujian Province (2016RCLKC)
This publication has 65 references indexed in Scilit:
- EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancerMolecular Cancer, 2012
- ID4 Imparts Chemoresistance and Cancer Stemness to Glioma Cells by Derepressing miR-9*–Mediated Suppression of SOX2Cancer Research, 2011
- Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancerBritish Journal of Cancer, 2011
- SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomasNature Genetics, 2009
- Causes and consequences of microRNA dysregulation in cancerNature Reviews Genetics, 2009
- Multiple roles for Sox2 in the developing and adult mouse tracheaDevelopment, 2009
- Deregulation of Scribble Promotes Mammary Tumorigenesis and Reveals a Role for Cell Polarity in CarcinomaCell, 2008
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007
- Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapyBritish Journal of Cancer, 2007
- Oncomirs — microRNAs with a role in cancerNature Reviews Cancer, 2006