# Unveiling the intricacies: small interfering RNA targeting Snail-1 unravels dynamics in endometrial carcinoma cell behavior

**Authors:** Feng Li, Yuanyuan Zhi, Yinghui Wang, Shaik Althaf Hussain, Turki Mayudh Alrubie, Ping Yang

PMC · DOI: 10.3389/fonc.2025.1567493 · 2025-06-12

## TL;DR

This study shows that silencing Snail-1 with siRNA reduces cancer cell invasion and metastasis in endometrial carcinoma by altering key genes and proteins.

## Contribution

The novel contribution is demonstrating the therapeutic potential of Snail-1 siRNA in modulating EMT and metastasis in endometrial carcinoma cells.

## Key findings

- Snail-1 siRNA significantly reduced Snail-1, MMP-9, Vimentin, and Notch1 expression while increasing E-cadherin.
- Silencing Snail-1 increased apoptosis and reduced migration in HEC-1A cells.
- ERK and AKT mRNA levels decreased, and miR-34a levels increased following Snail-1 silencing.

## Abstract

Investigated within the endometrial carcinoma (EC) context, Snail-1 emerges as a pivotal transcription factor governing invasion and metastasis by orchestrating epithelial-to-mesenchymal transition (EMT). Employing small interfering RNA (siRNA) to silence Snail-1 expression in the HEC-1A cell line, this study explored the repercussions on the expression of genes implicated in metastasis, cellular cytotoxicity, apoptosis, and migration.

HEC-1A cells were transfected with Snail-1-specific siRNA. Quantitative Real-time PCR was utilized to quantify the mRNA levels of Snail-1, Matrix metalloproteinase-9 (MMP-9), Vimentin, E-cadherin, Notch1, ERK, AKT, and miR-34a. Western blot analysis was also performed to ascertain alterations in Snail-1, MMP-9, Vimentin, E-cadherin, and Notch1 protein levels. Cytotoxicity of transfected cells was assessed via the MTT assay, while flow cytometry was employed to measure apoptosis. Migration was evaluated using a wound healing assay.

Transfection with 60 pmol/mL of Snail-1-specific siRNA significantly reduced Snail-1 expression at both the mRNA and protein levels. This was accompanied by decreased MMP-9, Vimentin, and Notch1 expression and increased E-cadherin expression, all confirmed at both transcript and protein levels. Furthermore, gene expression analysis revealed a downregulation of ERK and AKT mRNA levels and an upregulation of miR-34a. Moreover, transfection correlated with increased apoptosis and decreased migration of treated HEC-1A cells.

The study emphasizes the significant influence of Snail-1 on EMT in EC cells, thereby impacting apoptosis and metastasis. Targeted silencing of Snail-1 through specific siRNA emerges as a promising therapeutic approach in treating EC.

## Linked entities

- **Genes:** SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615], MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318], PRELID1 (PRELI domain containing 1) [NCBI Gene 737446], shg (shotgun) [NCBI Gene 37386], NOTCH1 (notch receptor 1) [NCBI Gene 4851], EPHB2 (EPH receptor B2) [NCBI Gene 2048], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], MIR34A (microRNA 34a) [NCBI Gene 407040]
- **Diseases:** endometrial carcinoma (MONDO:0002447)

## Full-text entities

- **Genes:** MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, VIM (vimentin) [NCBI Gene 7431], MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}
- **Diseases:** EC (MESH:D016889), metastasis (MESH:D009362), Cytotoxicity (MESH:D064420)
- **Chemicals:** MTT (MESH:C070243)
- **Cell lines:** HEC-1A — Homo sapiens (Human), Type II endometrial adenocarcinoma, Cancer cell line (CVCL_0293)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12197919/full.md

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Source: https://tomesphere.com/paper/PMC12197919