NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1

Shan, Jijun; Jiang, Wangjie; Chang, Jiang; Zhou, Tao; Chen, Yananlan; Zhang, Yaodong; Wang, Jifei; Wang, Yuming; Wang, Yirui; Xu, Xiao; Liu, Shuochen; Shi, Xiaoli; Fan, Shilong; Chen, Ruixiang; Li, Changxian; Li, Xiangcheng

doi:10.7150/ijbs.80737

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Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

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Int J Biol Sci 2023; 19(5):1336-1351. doi:10.7150/ijbs.80737 This issue Cite

Research Paper

NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1

Jijun Shan^#, Wangjie Jiang^#, Jiang Chang^#, Tao Zhou^#, Yananlan Chen, Yaodong Zhang, Jifei Wang, Yuming Wang, Yirui Wang, Xiao Xu, Shuochen Liu, Xiaoli Shi, Shilong Fan, Ruixiang Chen, Changxian Li^✉, Xiangcheng Li^✉

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University
# These authors contributed to the work equally and should be regarded as co-first authors.

Citation:

Shan J, Jiang W, Chang J, Zhou T, Chen Y, Zhang Y, Wang J, Wang Y, Wang Y, Xu X, Liu S, Shi X, Fan S, Chen R, Li C, Li X. NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1. Int J Biol Sci 2023; 19(5):1336-1351. doi:10.7150/ijbs.80737. https://www.ijbs.com/v19p1336.htm

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Abstract

Cholangiocarcinoma (CCA) is the second most common primary hepatic malignancy and associated with poor prognosis. Lack of therapeutic methods for CCA and insensitivity of targeted therapy and immunotherapy make its treatment challenging. NUF2, a component of Ndc80 kinetochore complex, is implicated in the initiation and development of multiple cancers. However, the role and mechanism of NUF2 in CCA is still unclear. In this research, we investigated the biological processes and underlying mechanisms of NUF2 in CCA. We discovered that the expression of NUF2 was upregulated in CCA and negatively correlated with prognosis. Changes in NUF2 levels had an impact on cell proliferation and migration. Moreover, NUF2 functioned as an oncogene to promote the progression of CCA through p38/MAPK signaling by inhibiting p62 binding of TFR1 and affecting its autophagic degradation. In addition, TFR1 promoted CCA progression and Kaplan-Meier analyses uncovered patients with high expression of TFR1 was associated with the poor survival. In conclusion, our study demonstrated that NUF2 promoted CCA progression by regulating TFR1 protein degradation, and the NUF2/TFR1/MAPK axis could be an excellent therapeutic target for CCA.

Keywords: Cholangiocarcinoma, NUF2, TFR1, MAPK, Autophagy

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APA

Shan, J., Jiang, W., Chang, J., Zhou, T., Chen, Y., Zhang, Y., Wang, J., Wang, Y., Wang, Y., Xu, X., Liu, S., Shi, X., Fan, S., Chen, R., Li, C., Li, X. (2023). NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1. International Journal of Biological Sciences, 19(5), 1336-1351. https://doi.org/10.7150/ijbs.80737.

ACS

Shan, J.; Jiang, W.; Chang, J.; Zhou, T.; Chen, Y.; Zhang, Y.; Wang, J.; Wang, Y.; Wang, Y.; Xu, X.; Liu, S.; Shi, X.; Fan, S.; Chen, R.; Li, C.; Li, X. NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1. Int. J. Biol. Sci. 2023, 19 (5), 1336-1351. DOI: 10.7150/ijbs.80737.

NLM

CSE

Shan J, Jiang W, Chang J, Zhou T, Chen Y, Zhang Y, Wang J, Wang Y, Wang Y, Xu X, Liu S, Shi X, Fan S, Chen R, Li C, Li X. 2023. NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1. Int J Biol Sci. 19(5):1336-1351.

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