Title: Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy

Abstract

Background Chemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance. Methods One hundred thirty‐one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interference was used to knock down the HOXA13 expression in KYSE70 and transfected HOXA13 plasmid to overexpress HOXA13 in KYSE510 cells. We examined half‐maximal inhibitory concentration of cisplatin, apoptosis, and epithelial‐to‐mesenchymal transition (EMT) in ESCC cell lines with different HOXA13 expression levels by cell counting kit‐8, flow cytometry, and transwell analysis. Results The median survival of patients with high HOXA13 expression was significantly shorter than those with low expression ( P  = 0.027). HOXA13 was associated with worse tumor regression grade ( P  = 0.009). Low HOXA13 expressed cells decreased the half‐maximal inhibitory concentration of cisplatin ( P  < 0.05), increased cisplatin‐induced apoptosis ( P  < 0.05), and decreased EMT ( P  < 0.05) compared with high HOXA13 expressed cells. In low HOXA13 expressed cells, cleaved caspase‐3 and cleaved PARP expression induced by cisplatin increased, while expression of E‐cadherin and Snail protein, markersmore » of EMT, was upregulated and downregulated, respectively. EMT decreased in low HOXA13 expressed cells. Conclusion High HOXA13 expression was associated with inferior tumor regression grade and poor overall survival in ESCC patients treated with neoadjuvant chemotherapy. HOXA13 increased cisplatin‐resistance and promoted EMT in ESCC cells.« less

Authors:

Shi, Qi ^[1]; Shen, Luyan ^[1]; Dong, Bin ^[2]; Fu, Hao ^[1]; Kang, Xiaozheng ^[1]; Dai, Liang ^[1]; Yang, Yongbo ^[1]; Yan, Wanpu ^[1]; Chen, Ke‐Neng  ^[1]

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+ Show Author Affiliations

1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I Peking University Cancer Hospital &, Institute Beijing China
2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology Peking University Cancer Hospital &, Institute Beijing China

Publication Date:

Mon May 14 00:00:00 EDT 2018

Sponsoring Org.:

USDOE

OSTI Identifier:

1437069

Alternate Identifier(s):

OSTI ID: 1458578

Resource Type:

Published Article

Journal Name:

Thoracic Cancer

Additional Journal Information:

Journal Name: Thoracic Cancer Journal Volume: 9 Journal Issue: 7; Journal ID: ISSN 1759-7706

Publisher:

Wiley-Blackwell

Country of Publication:

Australia

Language:

English