AI Article Synopsis
- Radiotherapy is crucial in treating locally advanced rectal cancer (LARC) but faces challenges due to radioresistance.
- The study identified SGK1 as a significant factor in LARC radioresistance by analyzing tumor samples from 110 patients, revealing its high expression in patients with poor treatment response.
- Inhibition of SGK1, regulated by ATF3, was shown to reduce radioresistance, suggesting potential strategies for improving treatment effectiveness through targeted therapies.
Article Abstract
Radiotherapy (RT) is a key component of neoadjuvant chemoradiotherapy to treat locally advanced rectal cancer (LARC). However, the therapeutic effect is limited due to radioresistance. Investigating the biomarkers of radioresistance might assist in the development of more effective therapeutic strategies for LARC.In this study, we investigated the different gene expressions in tumor samples from 110 patients using transcriptome analysis and immunohistochemistry (IHC), and identified serum- and glucocorticoid-regulated kinase 1 (SGK1) as a modulator of LARC radioresistance. We evaluated the impact of genetic and pharmacologic inhibition of the gene associated with radioresistance in vitro and in vivo. We found that the expression of SGK1 was upregulated in non-pathological complete response (non-pCR) patients. A high SGK1 expression was associated with radioresistance, whereas the genetic or pharmacologic inhibition of SGK1 expression reduced the radioresistance. We found that activate transcription factor 3 (ATF3) is a regulator of SGK1 in radioresistance.In conclusion, our findings indicate that SGK1 is a key player in LARC radioresistance, and drives radioresistance in an ATF3 dependent manner, which provides insights for future radio-sensitizer design.
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| http://dx.doi.org/10.1016/j.biopha.2020.109954 | DOI Listing |
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