Journal
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 55, Issue 2, Pages 304-313Publisher
SCIENCE PRESS
DOI: 10.3724/abbs.2022182
Keywords
colorectal cancer; DNA damage response; HOTTIP; HOXA13; neoadjuvant therapy
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The expression of HOXA13 is negatively associated with tumor regression and progression-free survival in patients with advanced colorectal cancer who undergo neoadjuvant therapy. Silencing HOXA13 enhances chemosensitivity and leads to increased apoptosis and DNA damage response in colorectal cancer cells, while overexpression of HOXA13 causes increased chemoresistance.
Neoadjuvant therapy (NAT) for advanced colorectal cancer (ACRC) is a kind of well-evidenced therapy, yet a portion of ACRC patients have poor therapeutic response. To date, no suitable biomarker used for assessing NAT efficacy has been reported. Here, we collect 72 colonoscopy biopsy tissue specimens from ACRC patients before undergoing NAT and investigate the relationship between HOXA13 expression and NAT efficacy. The results show that HOXA13 expression in pretreated tumor specimens is negatively associated with tumor regression (P < 0.001) and progression-free survival (P < 0.05) in ACRC patients who underwent NAT. Silencing of HOXA13 or its regulator HOTTIP significantly enhances the chemosensitivity of colorectal cancer (CRC) cells, leading to an increase in cell apoptosis and the DNA damage response (DDR) to chemotherapeutic drug treatment. In contrast, HOXA13 overexpression causes a significant increase in chemoresistance in CRC cells. In summary, we find that the HOTTIP/HOXA13 axis is involved in regulating chemotherapeutic sensitivity in CRC cells by modulating the DDR and that HOXA13 serves as a promising marker for NAT efficacy prediction in ACRC patients.
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