Abstract
Long noncoding RNA UCA1 has emerged as a novel regulator in cancer initiation and progression of various cancers. However, function and underlying mechanism of UCA1 in the progression of gastric cancer (GC) remain unclear. In the present study, we report that UCA1 expressed highly in GC tissues and GC cells, which was partly induced by SP1. UCA1 promoted GC cell proliferation and G1/S transition in vitro and in vivo. Moreover, UCA1 exerted its function through interacting with EZH2, promoting direct interaction with cyclin D1 promoter to activate the translation of cyclin D1. Furthermore, AKT/GSK-3B/cyclin D1 axis was activated to upregulate cyclin D1 due to overexpression of UCA1. In addition, EZH2 and phosphorylated AKT induced by UCA1 could impact each other to form a positive feedback to promote cyclin D1 expression. This study demonstrated that UCA1 as a critical regulator involved in GC proliferation and cell cycle progression by promoting cyclin D1 expression, which indicates that it may be clinically a potential therapeutic target in GC.
Highlights
Gastric cancer (GC) has been a heavy health burden worldwide especially in eastern Asia because of high incidence rates and mortality rates, which is the third leading cause of tumor death.[1]
The aim of the study was to figure out the following questions: (i) expression level of Urothelial cancer associated 1 (UCA1) in GC and the role in GC; (ii) the reason accounting for upregulation of UCA1 in GC; (3) potential downstream target and pathway of UCA1 involved in proliferation in gastric cancer
LncRNA UCA1 has been determined to be upregulated in multiple cancers including GC.[13,27,28]
Summary
Gastric cancer (GC) has been a heavy health burden worldwide especially in eastern Asia because of high incidence rates and mortality rates, which is the third leading cause of tumor death.[1]. More and more evidences demonstrated that dysregulation of lncRNAs could be a novel gap to understand the misbehavior of cancer in proliferation metastasis and metabolism.[7,8] LncRNAs could have multi-roles including oncogenes or tumor suppressor in regulating the initiation and progression of cancer. Urothelial cancer associated 1 (UCA1) was initially discovered and investigated in bladder cancer, which has oncogenic roles in tumor proliferation and metastasis.[9,10]. The aim of the study was to figure out the following questions: (i) expression level of UCA1 in GC and the role in GC; (ii) the reason accounting for upregulation of UCA1 in GC; (3) potential downstream target and pathway of UCA1 involved in proliferation in gastric cancer
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