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NSUN5-FTH1 Axis Inhibits Ferroptosis to Promote the Growth of Gastric Cancer Cells

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Abstract

Recent studies revealed that NOP2/Sun RNA methyltransferase 5 (NSUN5) - ferritin heavy chain (FTH1) pathway is associated with ferroptosis in stem cells, whereas its roles in gastric cancer are still unclear. Our study aims to investigate the roles of the NSUN5-FTH1 axis in gastric cancer (GC) and its molecular mechanisms. Stable cell lines were constructed on SGC7901 cells by using shRNAs and pcDNA3.1 expression vectors, respectively. CCK-8 kits were used to determine cell viability. Biochemicals assays were used to detect lipid reactive oxygen species (ROS) and intracellular Fe2+ levels. RNA immunoprecipitation assay, qPCR, and Western blotting were used to determine the changes in biomarkers. GC xenograft mouse model was established to confirm the observation in vivo. An elevation of NSUN5 was observed in GC tumor tissues. NSUN5 inhibited ferroptosis including decreasing cell viability and increasing levels of lipid ROS and Fe2+ in GC cells. Besides, a positive correlation was also observed between NSUN5 and FTH1. Interestingly, NSUN5 regulated the levels of FTH1, instead of FTH1 regulating NSUN5 in GC cells. NSUN5-FTH1 axis regulated erastin-induced ferroptosis in SGC7901 cells. Consistently, silencing NSUN5 or FTH1 inhibited the growth of the SGC7901 tumor in vivo. NSUN5-FTH1 axis promoted the growth of GC cells in part by the regulation of ferroptosis.

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Data Availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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Author notes

  1. These authors contributed equally: Yibin Su, Jiangrui Liu

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Quanzhou First Hospital affiliated to Fujian Medical University, No. 248 East Street, Licheng District, Quanzhou, 362000, Fujian, China

    Yibin Su, Jiangrui Liu, Zhihua Zheng, Liangpan Shi, Wenchang Huang, Xiaohui Huang, Chengwei Ye, Jinyu Qi, Weidong Wang & Haibin Zhuang

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  1. Yibin Su
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by J.L., Z.Z., L.S., W.H., X.H., C.Y., J.Q., W.W., H.Z. The first draft of the manuscript was written by Y.S. All authors read and approved the final manuscript.

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Correspondence to Yibin Su.

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The authors declare no competing interests.

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Current study is available from the corresponding author on reasonable request.

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The study was approved by the ethics committee of Quanzhou First Hospital, affiliated to Fujian Medical University. This study was performed in strict accordance with the NIH guidelines for the care and use of laboratory animals (NIH Publication No. 85-23 Rev. 1985).

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Su, Y., Liu, J., Zheng, Z. et al. NSUN5-FTH1 Axis Inhibits Ferroptosis to Promote the Growth of Gastric Cancer Cells. Cell Biochem Biophys 81, 553–560 (2023). https://doi.org/10.1007/s12013-023-01152-1

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  • DOI: https://doi.org/10.1007/s12013-023-01152-1

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