WBSCR22 and TRMT112 synergistically suppress cell proliferation, invasion and tumorigenesis in pancreatic cancer via transcriptional regulation of ISG15.

Abstract

Pancreatic cancer (PC) is one of the most aggressive and devastating types of cancer owing to its poor prognosis and deadly characteristics. It is well established that aberrations in the expression of key regulatory genes, namely tumor suppressors and oncogenes, predispose patients to progression and metastasis of PC. Upregulation of Williams‑Beuren syndrome chromosomal region 22 (WBSCR22) expression, a ribosomal biogenesis factor, has been reported in multiple types of human cancer. However, the role of WBSCR22 and its underlying mechanism in PC have not been well investigated. In the present study, the tumor suppressive role of WBSCR22 was reported in PC for the first time; the results indicated that WBSCR22 overexpression (OE) significantly suppressed cellular proliferation, migration, invasion and tumorigenesis in vivo and in vitro. RNA‑sequencing analysis revealed that WBSCR22 negatively regulated the transcription of interferon‑stimulated gene 15 (ISG15) downstream, which is a ubiquitin‑like modifier protein involved in metabolic and proteasome degradation pathways, while the antitumor function of WBSCR22‑OE could be rescued by ISG15 OE. In addition, the oncogenic role of ISG15 was further confirmed in PC; its upregulation promoted the proliferation, migration, invasion and tumorigenesis of PC. Furthermore, WBSCR22 and its cofactor tRNA methyltransferase activator subunit 11‑2 (TRMT112) functioned synergistically in PC, and concurrent ectopic OE of WBSCR22 and TRMT112 further promoted the tumor suppressive potential of WBSCR22 in PC. Collectively, the findings indicated that WBSCR22 played an important role in PC development and that the WBSCR22/ISG15 axis may provide a novel therapeutic strategy for PC treatment.

• Authors: Aamir Ali Khan, Hua Huang, Yue Zhao, Huan Li, Ruining Pan, Sijia Wang, Xinhui Liu
• Journal: International journal of oncology (Int J Oncol) Vol. 60 Issue 3 (03 2022) ISSN: 1791-2423 [Electronic] Greece
• PMID: 35088887 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Ubiquitins
• ISG15 protein, human
• BUD23 protein, human
• Methyltransferases
• TRMT112 protein, human

Topics

• Carcinogenesis (drug effects)
• Cell Line (drug effects, physiology)
• Cell Movement (drug effects, genetics)
• Cell Proliferation (drug effects, physiology)
• Cytokines (drug effects)
• Humans
• Methyltransferases (metabolism, pharmacology)
• Pancreatic Neoplasms (drug therapy, genetics)
• Ubiquitins (drug effects)