Dataset Information

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10-ERK signaling.

ABSTRACT: The chromobox (CBX) proteins mediate epigenetic gene silencing and have been implicated in the cancer development. By analyzing eight CBX family members in TCGA dataset, we found that chromobox 7 (CBX7) was the most strikingly downregulated CBX family member in urinary bladder cancer (UBC), as compared to normal tissues. Though dysregulation of CBX7 has been reported in multiple cancers, its specific role and clinical relevance in UBC remain unclear. Herein, we found that frequent downregulation of CBX7 in UBC specimens, which was due to its promoter hypermethylation, was correlated with poor prognosis. The ectopic expression of CBX7 suppressed UBC cell proliferation, migration, invasion, and cancer stemness, whereas CBX7 depletion promoted cancer cell aggressiveness. Importantly, CBX7 overexpression in UBC cells inhibited tumorigenicity, whereas CBX7 depletion promoted the tumor development, indicating its tumor-suppressive role in UBC. Using RNA-seq and chromosome immunoprecipitation (ChIP) assays, we identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of CBX7, which was negatively modulated by CBX7 in a PRC1-dependent manner and involved in stimulating ERK signaling. Consistently, AKR1B10 overexpression induced cancer cell aggressiveness, whereas suppression of AKR1B10 by siRNA or its small molecular inhibitor, oleanolic acid, reversed the CBX7 deficiency-induced cellular effects. AKR1B10 overexpression was negatively associated with CBX7 downregulation and predicted poor clinical outcomes in UBC patients. Taken together, our results indicate that CBX7 functions as a tumor suppressor to downregulate AKR1B10 and further inactivates ERK signaling. This CBX7/AKR1B10/ERK signaling axis may provide a new therapeutic strategy against UBC.

SUBMITTER: Huang Z

PROVIDER: S-EPMC8149849 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Transmembrane protein 229A (TMEM229A) is a member of the TMEM family that plays an important role in tooth differentiation and development. However, the expression level and biological role of TMEM229A in cancer remains unknown. The present study aimed to investigate the expression level of TMEM229A in non‑small cell lung cancer (NSCLC), as well as its effect and mechanism on NSCLC progression. Clinical specimens from patients with NSCLC were enrolled from the First People's Hospital of Huzhou (Huzhou, China). TMEM229A expression was detected using reverse transcription‑quantitative PCR (RT‑qPCR), western blotting and immunohistochemical analysis. The relationship between TMEM229A expression and the survival rate of patients with NSCLC was analyzed using Kaplan‑Meier Plotter datasets. The effects of TMEM229A on cell proliferation, migration and invasion were detected using Cell Counting Kit‑8, colony formation, soft agar, real‑time cellular analysis and Transwell assays. The expression levels of epithelial‑mesenchymal transition (EMT)‑related proteins, as well as ERK and AKT phosphorylation were determined via RT‑qPCR and western blot analysis. The results demonstrated that TMEM229A expression was significantly downregulated in human NSCLC tissues and in several cell lines compared with adjacent normal lung tissues and BEAS‑2B cells, respectively. Survival analysis of lung adenocarcinoma and squamous cell lung carcinoma cases identified that low TMEM229A expression was associated with a poor prognosis. The in vitro assays indicated that overexpressing TMEM229A significantly inhibited cell proliferation, migration and invasion, while TMEM229A knockdown had the opposite effect. Mechanistically, TMEM229A overexpression effectively increased E‑cadherin expression and reduced N‑cadherin, snail family transcriptional repressor 1 and MMP2 expression, indicating that EMT was suppressed. In addition, overexpression of TMEM229A reduced the expression levels of phosphorylated (p)‑ERK and p‑AKT, and this effect was partially suppressed by the incorporation of specific ERK inhibitor PD98059. Collectively, the results of the present study demonstrated that the effects of TMEM229A on inhibiting cell proliferation, migration and invasion were partially mediated by inactivating the ERK signaling pathway, thereby providing a potential therapeutic target for the treatment of NSCLC.

Dataset Information

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10-ERK signaling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets