The role and regulation mechanism of HYOU1 in the pathogenesis and development of pancreatic cancer
10.19405/j.cnki.issn1000-1492.2024.08.010
- VernacularTitle:HYOU1在胰腺癌发生发展中的作用及其调控机制
- Author:
Jialu DING
1
;
Beicheng SUN
Author Information
1. 南京中医药大学鼓楼临床医学院肝胆外科,南京 210008
- Keywords:
HYOU1;
pancreatic cancer;
PI3K/Akt signaling pathway
- From:
Acta Universitatis Medicinalis Anhui
2024;59(8):1354-1361
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which human hypoxia up-regulation 1(HYOU1)regulates pancreatic cancer development.Methods Bioinformatic and immunohistochemical staining analyses of HYOU1 ex-pression level in pancreatic tumor tissues,normal and paracancerous tissues and its correlation with patients'surviv-al.Quantitative real-time PCR(qPCR)and Western blot were used to clarify the expression level of HYOU1 in a number of human pancreatic ductal adenocarcinoma cell lines and a normal human pancreatic ductal cell line.Two cell lines with the highest expression levels of HYOU1,BXPC-3 and Panc-1,were selected to knock out HYOU1 by CRISPR-Cas9,and then cell survival,proliferation and migration of these cells were examined by cell counting kit-8(CCK-8),colony formation assay and wound healing experiment separately,as well as apoptosis was detected by flow cytometry.Subsequently,the protein levels of the PI3K/Akt signaling including PI3K,p-PI3K,Akt,and p-Akt were detected by Western blot in parental and HYOU1-ablated BXPC-3 and Panc-1 cells.Cell proliferation was also examined in HYOU1-ablated cells after treatment of recilisib,an activator of the PI3K/Akt pathway.Results The expression of HYOU1 in pancreatic tumor tissues was significantly higher than that in normal tissues,and the patients with high expression of HYOU1 had a much shorter survival compared to the patients with low HYOU1(P＜0.01).Immunohistochemical staining of pancreatic cancer specimens showed that the expression of HYOU1 was higher in tumor tissues than in paracancerous tissues(P＜0.01).The mRNA and protein levels of HYOU1 were higher in all pancreatic cancer cell lines compared to the human normal pancreatic ductal cell(P＜0.001,P＜0.01).HYOU1 ablation inhibited BXPC-3 and Panc-1 cells survival,proliferation and migration,and promoted early cell apoptosis.In addition,loss of HYOU1 decreased PI3K/Akt signaling activity,whereas the PI3K/Akt ac-tivator Recilisib reversed the effects of HYOU1 ablation on cell survival and proliferation.Conclusion HYOU1 promotes pancreatic cancer progression by activating the PI3K/Akt signaling pathway.
