Long noncoding RNAs (lncRNAs) have been demonstrated to play a role in carcinogenesis, but their mechanisms of function remain elusive. We explored the mechanisms of the oncogenic role of GCAWKR in gastric cancer (GC) using human tissues and cell lines. The in situ hybridization analysis was utilized to determine GCAWKR levels in samples from 42 GC patients and real-time qPCR in tissues from 123 patients. The GCAWKR levels were modulated in GC cell lines, and relevant biological and molecular analyses were performed. Levels of the GCAWKR were upregulated in GC tissues compared with normal tissues and associated with tumor size, lymph node metastasis, TNM stage, and patient outcomes. GCAWKR affected cell proliferation and cell invasion in multiple GC models. Mechanistically, GCAWKR bound WDR5 and KAT2A and acted as a molecular scaffold of WDR5/KAT2A complexes, modulating the affinity for WDR5/KAT2A complexes in the target gene''s promoter region. Thus, our data defined a mechanism of lncRNA-mediated carcinogenesis in GC, suggesting new therapeutic targets in GC.
[1]Fudan Univ, Shanghai Canc Ctr, Dept Gastr Surg, 270 Dongan Rd, Shanghai 200032, Peoples R China.
[2]Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China.
[3]Wannan Med Coll, Affiliated Hosp 1, Yijishan Hosp, Dept Gastroenterol, Wuhu, Anhui, Peoples R China.
[4]Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gen Surg, Shanghai, Peoples R China.
[5]Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, State Key Lab Oncogenes & Related Genes,Div Gastr, Shanghai, Peoples R China.
[6]Wenzhou Med Univ, Wenzhou Peoples Hosp, Wenzhou Clin Inst 3, Dept Gen Surg, 57 Canghou St, Wenzhou 325000, Zhejiang, Peoples R China.
[7]Wannan Med Coll, Affiliated Hosp 1, Cent Lab, Yijishan Hosp, 2 West Zheshan Rd, Wuhu 241001, Anhui, Peoples R China.
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