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PITPNC1 fuels radioresistance of rectal cancer by inhibiting reactive oxygen species production

Neoadjuvant radiotherapy is a commonly used method for the current standard-of-care for most patients with rectal cancer, when the effects of radioresistance are limited. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1), a lipid-metabolism-related gene, has previously been proved t...

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Published in:Annals of translational medicine 2020-02, Vol.8 (4), p.126-126
Main Authors: Tan, Yujing, Shao, Ruoyang, Li, Jingyu, Huang, Hongyun, Wang, Yanru, Zhang, Menglan, Cao, Jianyun, Zhang, Junde, Bu, Junguo
Format: Article
Language:English
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Summary:Neoadjuvant radiotherapy is a commonly used method for the current standard-of-care for most patients with rectal cancer, when the effects of radioresistance are limited. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1), a lipid-metabolism-related gene, has previously been proved to manifest pro-cancer effects in multiple types of cancer. However, whether PITPNC1 plays a role for developing radioresistance in rectal cancer patients is still unknown. Therefore, this study aims to investigate the role of PITPNC1 in rectal cancer radioresistance. Patient-derived tissue were used to detect the difference in the expression level of PITPNC1 between radioresistant and radiosensitive patients. Bioinformatic analyses of high-throughput gene expression data were applied to uncover the correlations between PITPNC1 level and oxidative stress. Two rectal cancer cell lines, SW620, and HCT116, were selected to investigate the effect of PITPNC1 on radioresistance, reactive oxygen species (ROS) generation, apoptosis, and proliferation in rectal cancer. PITPNC1 is highly expressed in radioresistant patient-derived rectal cancer tissues compared to radiosensitive tissue; therefore, PITPNC1 inhibits the generation of ROS and improves the extent of radioresistance of rectal cancer cell lines and then inhibits apoptosis. Knocking down PITPNC1 facilitates the production of ROS while application of the ROS scavenger, N-acetyl-L-cysteine (NAC), could reverse this effect. PITPNC1 fuels radioresistance of rectal cancer via the inhibition of ROS generation.
ISSN:2305-5839
2305-5839
DOI:10.21037/atm.2020.02.37