Open Access

ARTICLE

The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma

by RUI ZHANG^1,2,#, PENG ZHOU^1,3,#, XIA OU⁴, PEIZHU ZHAO², XIJING GUO², MIAN XI^5,*, CHEN QING^1,*

1 School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650500, China
2 Department of Radiotherapy, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
3 Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China
4 Medical School, Kunming University of Science and Technology, Kunming, 650504, China
5 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China

* Corresponding Authors: MIAN XI. Email: ; CHEN QING. Email:
# Rui Zhang and Peng Zhou have contributed equally to this work

(This article belongs to the Special Issue: Application of Multi-omics Analysis in Cancer Immunotherapy)

Oncology Research 2023, 31(6), 887-897. https://doi.org/10.32604/or.2023.030184

Received 25 March 2023; Accepted 14 June 2023; Issue published 15 September 2023

Abstract

Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in patients worldwide. Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC. It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC. Here, we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients. We found that DMRTA1 was extremely upregulated in the non-pathologic complete response (non-pCR) group. The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression, which could increase cisplatin sensitivity in ESCC. Additionally, suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells. Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2, which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback. Therefore, DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.

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Keywords

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