1. Academic Validation
  2. Dysregulation of pseudouridylation in small RNAs contributes to papillary thyroid carcinoma metastasis

Dysregulation of pseudouridylation in small RNAs contributes to papillary thyroid carcinoma metastasis

  • Cancer Cell Int. 2024 Oct 14;24(1):337. doi: 10.1186/s12935-024-03482-3.
Xi Wang # 1 2 Hengyuan Gao # 1 3 Wenjun Pu 1 Zhipeng Zeng 1 Nan Xu 1 Xunpeng Luo 1 Donge Tang 4 Yong Dai 5 6 7 8
Affiliations

Affiliations

  • 1 The First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen, 518055, China.
  • 2 The Fourth Clinical Medical College of Guangzhou, Shenzhen Traditional Chinese Medicine Hospital, University of Chinese Medicine, Shenzhen, 518033, China.
  • 3 Department of Thyroid Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
  • 4 The First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen, 518055, China. donge66@126.com.
  • 5 The First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen, 518055, China. daiyong22@aust.edu.cn.
  • 6 The Fourth Clinical Medical College of Guangzhou, Shenzhen Traditional Chinese Medicine Hospital, University of Chinese Medicine, Shenzhen, 518033, China. daiyong22@aust.edu.cn.
  • 7 The First Affiliated Hospital, School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China. daiyong22@aust.edu.cn.
  • 8 Peking University Shenzhen Hospital, Shenzhen, 518036, China. daiyong22@aust.edu.cn.
  • # Contributed equally.
Abstract

Background: Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.

Methods: We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.

Results: Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.

Conclusions: Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.

Keywords

Papillary thyroid cancer (PTC); Pseudouridylation (ψ); Small RNA; Tumor migration; pre-miRNA.

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