The prognostic value and mechanisms of lncRNA UCA1 in human cancer

Abstract

Long noncoding RNAs (lncRNAs), longer than 200 nucleotides in length, play important roles in the development and progression of various cancers. An increasing number of studies have revealed that lncRNAs function as potential oncogenes or tumor suppressors to influence biological processes, such as cell growth, invasion, migration and apoptosis. Urothelial carcinoma associated 1 (UCA1), an oncogenic lncRNA, was first found in bladder cancer and highly expressed in multiple cancers, including gastric cancer, colorectal cancer, lung cancer and breast cancer. UCA1 promotes tumorigenesis mainly via binding to tumor-suppressive microRNAs (miRNAs), activating several pivotal signaling pathways and alteration of epigenetic and transcriptional regulation. In addition, high expression of UCA1 is related to poor clinicopathological features especially for shorter overall survival, suggesting that UCA1 might be regarded as a prognosis biomarker in human cancers. In the present review, we summarized current studies on UCA1 to explore its prognostic value and underlying regulation mechanisms in the development of multiple cancers in order to provide a glimmer of hope for the prevention and treatment of malignant tumors.

Keywords: UCA1; cancer; lncRNA; mechanism; prognostic.

Figure 1

Regulating mechanisms of UCA1 in multiple human cancers. (A) UCA1 acted as a ceRNA to bind with miR-204-5p to increase the expression of CREB1, BCL2 and RAB22A. (B) UCA1 functioned as a ceRNA to bind with miR-204 to upregulate SOX4 expression level. (C) Increased UCA1 could upregulate N-cadherin and vimentin expression, while E-cadherin, an epithelial marker, was downregulated. (D) UCA1 served as an endogenous sponge of miR-143 to increase the expression of HMGB1 then promote EMT process. (E) Silencing UCA1 could repress the expression of FGFR1to inhibit the activation of ERK signaling pathway. (F) UCA1 could regulate the expression of β-catenin to activate Wnt/β-catenin signaling pathway. (G) The PI3K/AKT signaling pathway was activated when UCA1 was highly expressed.

Figure 2

Epigenetic and transcriptional regulation mechanisms of UCA1 in multiple human cancers. (A) UCA1 physically bound to EZH2 and suppressed transcription of P27 by histone methylation (H3K27me3) on the promoter of p27Kip1. (B) Transcription factor SP1 could activate UCA1 expression, and UCA1 physically combined with EZH2 to enhance the expression of cyclin D1. (C) TEAD·SMAD complexes promoted the level of UCA1.