NMI promotes tumor progression and gemcitabine resistance in pancreatic cancer via STAT3-IFIT3 axis.
Mol Carcinog
; 63(2): 195-208, 2024 Feb.
Article
in En
| MEDLINE
| ID: mdl-37846815
ABSTRACT
N-myc and STAT interactor (NMI) has been reported to interact with several transcription factors, including STATs family, c-Myc, N-Myc, and BRCA1, to indirectly affect transcription events and participate in multiple cellular processes. However, its function in pancreatic ductal adenocarcinoma (PDAC) has seldom been studied. In this study, we investigated the regulation of NMI on PDAC progression and uncovered the underlying molecular mechanisms. We found that NMI expression was significantly upregulated in PDAC and high NMI expression was related to a worse patient survival. Cell proliferation and migration assay, including cell viability, transwell assay, wound healing, and subcutaneous mouse model were utilized to confirm the function of NMI in PDAC progression. Downregulation of NMI abrogates tumor progression of PDAC both in vitro and in vivo. RNA sequencing was utilized to identify the downstream molecules of NMI and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) was confirmed to be regulated by NMI in both mRNA and protein level. The binding function of NMI to STAT3 was essential in regulating the IFIT3 expression. Moreover, the NMI/STAT3-IFIT3 axis was identified to markedly facilitate the gemcitabine resistance in PDAC cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Carcinoma, Pancreatic Ductal
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Carcinog
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2024
Type:
Article
Affiliation country:
China