DataVXAdvanced SciencePaper
journal article·2025-02Open access

RTN4IP1 Contributes to ESCC via Regulation of Amino Acid Transporters

Huifang Wei, Dengyun Zhao, Yafei Zhi, Qiong Wu, Jing Ma, Jialuo Xu, Tingting Liu, Jing Zhang, Penglei Wang, Yamei Hu, Xinyu He, Fangqin Guo, Ming Jiang, Dandan Zhang, Wenna Nie, Ran Yang, Tongjin Zhao, Zigang Dong, Kangdong Liu

Advanced Science· Volume 12· Issue 8
Publisher pageOpen full text
Source abstract

Abstract

Abstract Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of esophageal cancer cases. The lack of effective therapeutic targets makes it difficult to improve the overall survival of patients with ESCC. Reticulon 4 Interacting Protein 1 (RTN4IP1) is a novel mitochondrial oxidoreductase. Here, a notable upregulation of RTN4IP1 is demonstrated, which is associated with poor survival in patients with ESCC. RTN4IP1 depletion impairs cell proliferation and induces apoptosis of ESCC cells. Furthermore, c‐Myc regulates RTN4IP1 expression via iron regulatory protein 2 (IRP2) at the post‐transcriptional level. Mechanistically, RTN4IP1 mRNA harbors functional iron‐responsive elements (IREs) in the 3′ UTR, which can be targeted by IRP2, resulting in increased mRNA stability. Finally, RTN4IP1 depletion abrogates amino acid uptake and induces amino acid starvation via downregulation of the amino acid transporters SLC1A5, SLC3A2, and SLC7A5, indicating a possible pathway through which RTN4IP1 contributes to ESCC carcinogenesis and progression. In vivo studies using cell‐derived xenograft and patient‐derived xenograft mouse models as well as a 4‐nitroquinoline 1‐oxide‐induced ESCC model in esophageal‐specific Rtn4ip1 knockout mice demonstrate the essential role of RTN4IP1 in ESCC development. Thus, RTN4IP1 emerges as a key cancer‐promoting protein in ESCC, suggesting therapeutic RTN4IP1 suppression as a promising strategy for ESCC treatment.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Epigenetics and DNA Methylation · RNA modifications and cancer · Cancer, Hypoxia, and Metabolism

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pathophysiology School of Basic Medical Sciences Zhengzhou University, China‐US (Henan) Hormel Cancer Institute Zhengzhou 450000 China

Department of Pathophysiology School of Basic Medical Sciences, Zhengzhou University China‐US (Henan) Hormel Cancer Institute Chest Hospital of Zhengzhou University Zhengzhou 450000 China

Department of Pathophysiology School of Basic Medical Sciences Zhengzhou University Zhengzhou 450000 China

China‐US (Henan) Hormel Cancer Institute Zhengzhou 450000 China

Department of Pathophysiology School of Basic Medical Sciences Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou University Zhengzhou 450000 China

State Key Laboratory of Genetic Engineering Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative Biology Zhongshan Hospital Shanghai Qi Zhi Institute Fudan University Shanghai 200438 China

Department of Pathophysiology School of Basic Medical Sciences The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, State Key Laboratory of Esophageal Cancer Prevention and Treatment Provincial Cooperative Innovation Center for Cancer Chemoprevention China‐US (Henan) Hormel Cancer Institute, Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou University Zhengzhou 450000 China

References (64)

Show source-provided references
1. 10.1038/nrdp.2017.4810.1038/nrdp.2017.48 ↗
2. 10.1038/s41392-020-00323-310.1038/s41392-020-00323-3 ↗
3. 10.3892/ol.2020.1168510.3892/ol.2020.11685 ↗
4. 10.1001/jama.2021.1283610.1001/jama.2021.12836 ↗
5. 10.1016/S0140-6736(21)01234-410.1016/S0140-6736(21)01234-4 ↗
6. 10.1016/j.ccell.2022.02.00710.1016/j.ccell.2022.02.007 ↗
7. 10.1046/j.1471-4159.2002.00788.x10.1046/j.1471-4159.2002.00788.x ↗
8. 10.1001/jamaneurol.2017.206510.1001/jamaneurol.2017.2065 ↗
9. 10.1055/s-0040-170853910.1055/s-0040-1708539 ↗
10. 10.1016/j.ajhg.2015.09.01210.1016/j.ajhg.2015.09.012 ↗
11. 10.1038/jhg.2017.6810.1038/jhg.2017.68 ↗
12. 10.1093/brain/awac39510.1093/brain/awac395 ↗
13. 10.1007/s12031-019-01319-710.1007/s12031-019-01319-7 ↗
14. 10.1038/s41589-023-01452-w10.1038/s41589-023-01452-w ↗
15. 10.1210/jc.2012-318010.1210/jc.2012-3180 ↗
16. 10.1186/s12885-019-5554-z10.1186/s12885-019-5554-z ↗
17. 10.1186/s12920-021-00916-z10.1186/s12920-021-00916-z ↗
18. 10.1038/s41388-021-02099-410.1038/s41388-021-02099-4 ↗
19. 10.1038/s41467-021-25202-510.1038/s41467-021-25202-5 ↗
20. 10.1186/s12943-018-0915-910.1186/s12943-018-0915-9 ↗
21. 10.1016/j.neo.2017.05.00210.1016/j.neo.2017.05.002 ↗
22. 10.1158/1078-0432.CCR-10-272410.1158/1078-0432.CCR-10-2724 ↗
23. 10.1158/2159-8290.CD-12-009510.1158/2159-8290.CD-12-0095 ↗
24. 10.1016/j.cell.2012.03.00310.1016/j.cell.2012.03.003 ↗
25. 10.1158/2159-8290.CD-15-050710.1158/2159-8290.CD-15-0507 ↗
26. 10.1093/nar/gkx24710.1093/nar/gkx247 ↗
27. 10.1093/nar/gkq37110.1093/nar/gkq371 ↗
28. 10.1038/nrc349510.1038/nrc3495 ↗
29. 10.1016/j.bbamcr.2012.05.01010.1016/j.bbamcr.2012.05.010 ↗
30. 10.1126/science.283.5402.67610.1126/science.283.5402.676 ↗
31. 10.1038/s41586-019-1705-210.1038/s41586-019-1705-2 ↗
32. 10.1038/s41586-019-1707-010.1038/s41586-019-1707-0 ↗
33. 10.1073/pnas.212198711910.1073/pnas.2121987119 ↗
34. 10.1158/0008-5472.CAN-19-341510.1158/0008-5472.CAN-19-3415 ↗
35. 10.1158/0008-5472.CAN-19-065010.1158/0008-5472.CAN-19-0650 ↗
36. 10.3945/an.112.00211310.3945/an.112.002113 ↗
37. 10.1038/emboj.2010.8110.1038/emboj.2010.81 ↗
38. 10.1016/j.semcancer.2005.04.00510.1016/j.semcancer.2005.04.005 ↗
39. 10.1038/s41419-022-05526-w10.1038/s41419-022-05526-w ↗
40. 10.1158/1078-0432.CCR-12-233410.1158/1078-0432.CCR-12-2334 ↗
41. 10.1038/onc.2015.38110.1038/onc.2015.381 ↗
42. 10.1186/s40880-018-0288-x10.1186/s40880-018-0288-x ↗
43. 10.1074/jbc.M20157220010.1074/jbc.M201572200 ↗
44. 10.1111/acel.1294710.1111/acel.12947 ↗
45. 10.3892/or.2012.187810.3892/or.2012.1878 ↗
46. 10.1016/j.cmet.2015.12.00610.1016/j.cmet.2015.12.006 ↗
47. 10.1038/s41568-021-00378-610.1038/s41568-021-00378-6 ↗
48. 10.1038/nrclinonc.2016.6010.1038/nrclinonc.2016.60 ↗
49. 10.1183/13993003.00711-201610.1183/13993003.00711-2016 ↗
50. 10.1371/journal.pone.001016310.1371/journal.pone.0010163 ↗
51. 10.1158/0008-5472.CAN-13-122410.1158/0008-5472.CAN-13-1224 ↗
52. 10.1158/1078-0432.CCR-18-295110.1158/1078-0432.CCR-18-2951 ↗
53. 10.1038/s41588-020-00753-310.1038/s41588-020-00753-3 ↗
54. 10.1016/j.ejca.2013.11.01010.1016/j.ejca.2013.11.010 ↗
55. 10.1016/j.tibs.2018.05.00310.1016/j.tibs.2018.05.003 ↗
56. 10.1038/s41598-019-50547-910.1038/s41598-019-50547-9 ↗
57. 10.1016/j.bbrc.2023.06.05510.1016/j.bbrc.2023.06.055 ↗
58. 10.1038/s41556-020-0554-410.1038/s41556-020-0554-4 ↗
59. 10.3389/fimmu.2021.62432410.3389/fimmu.2021.624324 ↗
60. 10.1016/j.molcel.2020.09.00610.1016/j.molcel.2020.09.006 ↗
61. 10.1016/j.cell.2023.02.03710.1016/j.cell.2023.02.037 ↗
62. 10.1016/j.cell.2016.11.01310.1016/j.cell.2016.11.013 ↗
63. 10.1007/BF0030023410.1007/BF00300234 ↗
64. 10.1158/1078-0432.CCR-0999-310.1158/1078-0432.CCR-0999-3 ↗