Open AccessRAI14 silencing suppresses progression of esophageal cancer via the STAT3 pathway
Author(s) -
Jianlin Wang,
Yun Cai,
Judong Luo,
Zhiqiang Sun,
Jingping Yu,
Feng Yan,
Xia He
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.103613
Subject(s) - downregulation and upregulation , cyclin d1 , gene silencing , cancer research , oncogene , cell cycle , gene knockdown , cell growth , stat3 , apoptosis , biology , cancer , cell cycle checkpoint , gene , genetics
Esophageal cancer (EC) is an aggressive malignancy that has an unclear molecular pathogenesis. Although retinoic acid induced 14 (RAI14) is involved in various cancer processes, the relationship between EC and RAI14 has not been elucidated. Our study reported the oncogenic function of RAI14 and its underlying mechanisms in EC. The Cancer Genome Atlas (TCGA) database revealed that RAI14 was upregulated in EC, and this upregulation correlated with T stage, histologic grade, and poor clinical prognosis. RAI14 was evaluated in EC cell lines, and the overexpression of RAI14 promoted cell proliferation, migration, and invasion in vitro . Conversely, RAI14 knockdown induced apoptosis and cell cycle arrest. RAI14 activated STAT3, upregulated Mcl-1 and cyclin D1, and inhibited cleaved caspase-3. Inhibition of STAT3 restored the oncogenic effect of RAI14, and RAI14 silencing restrained tumor growth and the protein level of Ki67 in vivo . Our results suggest that RAI14 regulates the STAT3 pathway and acts as an oncogene during EC progression.