Background
The condensation complex gene non-SMC condensin I complex subunit G(NCAPG), a cell cycle-associated condensin, is over-expressed in various cancers. However, its biological function in colorectal cancer (CRC) has yet to be deciphered. In this study, we investigated the role of NCAPG in CRC progression.
Methods
Tissues and cells were used to measure NCAPG expression levels and their association with clinicopathological characteristics. NCAPG silencing and overexpression in CRC cells were used to measure its effect on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) progression. In addition, mRNA, and protein expression levels of key EMT biomarkers were measured. The underlying mechanism of NCAPG modulating CRC progression was further explored using western blotting, co-immunoprecipitation (CO-IP), and immunofluorescence (IF) assays.
Results
NCAPG was over-expressed in CRC tissues and cell lines. High expression levels were associated with differentiation levels, lymph metastasis, and vascular invasion in patients. NCAPG silencing suppressed, while NCAPG overexpression promoted the proliferative, migration, and invasive capacity of HCT116 and SW480 cells. Mechanistically, we discovered that NCAPG participated in regulating the EMT process and the Wnt/β-catenin signaling pathway to facilitate CRC invasion and metastasis. Additional experiments demonstrated that NCAPG activated the Wnt/β-catenin signaling pathway by binding to β-catenin in CRC cells.
Conclusion
NCAPG acts as an oncogene involved in the development and progression of CRC by binding to β-catenin to activate the Wnt/β-catenin signaling pathway.
The c-Myc oncoprotein plays a prominent role in cancer initiation, progression, and maintenance. Long noncoding RNAs (lncRNAs) are recently emerging as critical regulators of the c-Myc signaling pathway. Here, we report the lncRNA USP2-AS1 as a direct transcriptional target of c-Myc. Functionally, USP2-AS1 inhibits cellular senescence and acts as an oncogenic molecule by inducing E2F1 expression. Mechanistically, USP2-AS1 associates with the RNA-binding protein G3BP1 and facilitates the interaction of G3BP1 to E2F1 3′-untranslated region, thereby leading to the stabilization of E2F1 messenger RNA. Furthermore, USP2-AS1 is shown as a mediator of the oncogenic function of c-Myc via the regulation of E2F1. Together, these findings suggest that USP2-AS1 is a negative regulator of cellular senescence and also implicates USP2-AS1 as an important player in mediating c-Myc function.
p53 plays a central role in tumor suppression. Emerging evidence suggests long noncoding RNA (lncRNA) as an important class of regulatory molecules that control the p53 signaling. Here, we report that the oncogenic lncRNA E2F1 messenger RNA (mRNA) stabilizing factor (EMS) and p53 mutually repress each other’s expression. EMS is negatively regulated by p53. As a direct transcriptional repression target of p53, EMS is surprisingly shown to inhibit p53 expression. EMS associates with cytoplasmic polyadenylation element-binding protein 2 (CPEB2) and thus, disrupts the CPEB2–p53 mRNA interaction. This disassociation attenuates CPEB2-mediated p53 mRNA polyadenylation and suppresses p53 translation. Functionally, EMS is able to exert its oncogenic activities, at least partially, via the CPEB2–p53 axis. Together, these findings reveal a double-negative feedback loop between p53 and EMS, through which p53 is finely controlled. Our study also demonstrates a critical role for EMS in promoting tumorigenesis via the negative regulation of p53.
Eukaryotic translation initiation factor 4 (eIF4E) has been demonstrated to promote tumorigenesis in different types of cancer; however, whether eIF4E is involved in the development of GBC is unclear. The present study aimed to explore the biological function of eIF4E in gallbladder cancer (GBC) and identified that the expression level of eIF4E was significantly increased in GBC tissues compared with that in normal gallbladder tissues. The overall survival (OS) was also shorter in the group of patients with GBC with increased eIF4E expression. Increased eIF4E was correlated with advanced stage and higher histologic grade. Knockdown of eIF4E significantly inhibited cell proliferation, colony formation and cell cycle-associated protein expression levels in 2 GBC cell lines. The weight of the tumors in the eIF4E knockdown group was remarkably decreased compared with the control group. It also was revealed that knockdown of eIF4E is associated with upregulating cyclin-dependent kinase inhibitor 1B and down-regulating the expression levels of cyclin E1 and cyclin D1
in vitro
and
in vivo
. These data demonstrated that eIF4E is a novel prognostic marker in GBC and may serve a critical role in the regulation of cell proliferation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.