Affiliation:
1. Experimental Research Center, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University , 201700 , Shanghai , China
2. Experimental Research Center, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University , 1158 East Gongyuan Road, 201700 , Shanghai , China
Abstract
Abstract
Backgrounds
The integrator complex (INT) is a multiprotein assembly in gene transcription. Although several subunits of INT complex have been implicated in multiple cancers, the complex’s role in gastric cancer (GC) is poorly understood.
Methods
The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein–protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC.
Results
The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5′–3′ RNA polymerase activity. Moreover, these INT subunit expressions were associated with tumor-infiltrating lymphocytes and MSI in GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inhibits cell proliferation ability. INTS11 overexpression showed opposite effects.
Conclusions
Our data demonstrate that the INT complex might act as an oncogene and can be used as a prognosis biomarker for GC.