International Journal of Biological Sciences

Impact factor
4.057

ISSN 1449-2288

News feeds of IJBS published articles
Manuscript login
Account
Submit

open access Global reach, higher impact

Theranostics

International Journal of Medical Sciences

Journal of Cancer

Journal of Genomics

Journal of Bone and Joint Infection (JBJI)

Oncomedicine

Journal of Biomedicine

Nanotheranostics

PubMed Central Indexed in Journal Impact Factor

Int J Biol Sci 2018; 14(5):531-541. doi:10.7150/ijbs.23945

Research Paper

PARI functions as a new transcriptional target of FOXM1 involved in gastric cancer development

Yi Zhang1*, Xiaojuan Ye2*, Lizhi Chen3*, Qiong Wu1, Yong Gao1✉, Yandong Li1✉

1. Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China;
2. Department of Hematology & Oncology, the People's Hospital of Beilun District, Beilun Branch Hospital of the First Affiliated Hospital of Medical School of Zhejiang University, Ningbo 315800, China;
3. Department of Pharmacy, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China.
*These authors contributed equally to this work.

Abstract

PARI, an element of the homologous recombination pathway of DNA repair,is involved in the regulation of cell cycle and carcinogenesis in pancreatic cancer. However, little is known about the function and regulatory mechanism of PARI in other cancers. In the present study, we evaluated the expression of PARI in gastric cancer (GC) by immunohistochemical analysis in a tissue microarray and characterized its functions using in vitro assays and in vivo animal models. We found higher expression of PARI protein was shown in GC tissues compared with related adjacent normal gastric mucosa tissues. Knockdown of PARI by RNA inference decreased cell proliferation, migration, and invasion of GC cells in vitro, as well as reduced the xenograft tumor growth and lung metastasis formation in vivo. Quantitative real-time PCR and western blot results revealed that PARI expression was activated by a well-known oncogene FOXM1 and positively correlated with FOXM1 expression at mRNA level in 38 paired of GC samples. Luciferase reporter assay and chromatin immunoprecipitation assay further demonstrated that FOXM1 directly regulated PARI transcription by binding to the specific sequences of PARI promoter. In addition, PARI knockdown blocked the effect of FOXM1 on GC cell migration. Taken together, our results suggest that PARI plays potential oncogenic roles and functions as a transcriptional target and effector of FOXM1 in GC development.

Keywords: PARI, FOXM1, Gastric cancer, Proliferation, Migration

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Zhang Y, Ye X, Chen L, Wu Q, Gao Y, Li Y. PARI functions as a new transcriptional target of FOXM1 involved in gastric cancer development. Int J Biol Sci 2018; 14(5):531-541. doi:10.7150/ijbs.23945. Available from http://www.ijbs.com/v14p0531.htm