Downregulation of LNMAS orchestrates partial EMT and immune escape from macrophage phagocytosis to promote lymph node metastasis of cervical cancer.
Oncogene
; 41(13): 1931-1943, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35152264
ABSTRACT
Epithelial-mesenchymal transition (EMT) is an essential step to drive the metastatic cascade to lymph nodes (LNs) in cervical cancer cells. However, few of them metastasize successfully partially due to increased susceptibility to immunosurveillance conferred by EMT. The precise mechanisms of cancer cells orchestrate EMT and immune evasion remain largely unexplored. In this study, we identified a lncRNA termed lymph node metastasis associated suppressor (LNMAS), which was downregulated in LN-positive cervical cancer patients and correlated with LN metastasis and prognosis. Functionally, LNMAS suppressed cervical cancer cells metastasis in vitro and in vivo. Mechanistically, LNMAS exerts its metastasis suppressive activity by competitively interacting with HMGB1 and abrogating the chromatin accessibility of TWIST1 and STC1, inhibiting TWIST1-mediated partial EMT and STC1-dependent immune escape from macrophage phagocytosis. We further demonstrated that the CpG sites in the promoter region of LNMAS was hypermethylated and contributed to the downregulation of LNMAS. Taken together, our results reveal the essential role of LNMAS in the LN metastasis of cervical cancer and provide mechanistic insights into the regulation of LNMAS in EMT and immune evasion.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo do Útero
/
Transição Epitelial-Mesenquimal
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article