MPZL1 upregulation promotes tumor metastasis and correlates with unfavorable prognosis in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC), accounting for 85% of all lung cancer, is one of the leading causes of cancer-related death worldwide. Previously, we demonstrated that MPZL1 gene amplification promotes liver cancer metastasis through activating Src/Cortactin pathway. However, the clinical relevance and biological roles of the MPZL1 gene in lung cancer are still unknown. Here, we found that MPZL1 expression upregulates in human NSCLC, which is partly due to the copy number amplification of this gene. Next, we observed that high MPZL1 expression correlates with unfavorable prognosis of NSCLC patients. We further demonstrated that ectopic MPZL1 overexpression promotes in vitro migratory but not proliferation and colony formation abilities of both H1299 and H460 cells. Consistently, we found that MPZL1 knockdown impairs the migratory abilities of A549 and H1775 cells. Moreover, we found that MPZL1 knockdown inhibits in vivo metastatic but not tumor growth abilities of the A549 cells. Additionally, a total of 297 differentially expressed genes (DEGs) were identified by RNA sequencing in A549 cells upon MPZL1 knockdown. By integrative analysis of DEGs regulated by MPZL1 in A549 cells and human NSCLC tissues, we revealed that COL11A1 is the potential effector gene that positively regulated by MPZL1 and correlates with poor prognosis of NSCLC patients. In conclusion, our work indicates that one of the mechanisms by which MPZL1 promotes NSCLC metastasis is through upregulating the COL11A1, and MPZL1 can be used as a biomarker to predict the prognosis of NSCLC patients.

Analysis of cancer-associated fibroblasts related genes identifies COL11A1 associated with lung adenocarcinoma prognosis

“…We further verified the effect of COL11A1 on the prognosis of LUAD patients using the GSE72094 and Kaplan-Meier plotter databases and confirmed that the prognosis of LUAD patients with high expression of COL11A1 was poor. Feng et al demonstrated that COL11A1 is a potential effector gene that is positively regulated by MPZL1 and correlates with poor prognosis in LUAD patients [ 24 ]. Therefore, COL11A1 may be a potential prognostic biomarker in LUAD.…”

Exploring gastric cancer genetics: A turning point in common variable immunodeficiency

“…In our study, we also conducted an analysis of DGE with the aim of identifying the transcriptomic signature of CVID in GC samples. An enrichment was observed in pathways involved in the innate immune response against pathogen-associated molecular patterns and type 2 immune responses to parasites and protozoa in the distal small intestine and to viruses ( TAS1R3 and SYT1 , respectively) 51 , 52 , 53 , 54 ; DNA repair ( E2F7 ) 55 ; cell proliferation, migration, and invasion in several types of cancers ( MPZL1 ) 56 , 57 , 58 ; and regulation of cell cycle, inflammation, and host-defense response ( PGRN ). 59 , 60 , 61 …”

Genome-wide methylation profiling of Peripheral T-cell lymphomas identifies TRIP13 as a critical driver of tumor proliferation and survival

“…UHRF1 is overexpressed in T-cell ALL and its knockdown reduces c-MYC expression and viability in these malignancies 33 . Other genes hypomethylated and overexpressed in PTCL -RAB13, MPZL1, CDK14 -were implicated in tumor progression of several different tumors including B-cell lymphomas, and glioblastomas, lung and ovarian 34,35,46,47 . Among genes, we detected to be hypermethylated and silenced in PTCL are major tumor suppressors, e.g.…”

“…Several genes from this group, such as UHRF1, MPZL1, CDK14, RACGAP1, RAB13, and others have oncogenic functions in various solid tumors, leukemias, and lymphomas either predicting poor prognosis, involved in tumor migration, metastasis, or maintenance [31][32][33][34][35] .…”