SATB1 3′‐UTR and lncRNA‐UCA1 competitively bind to miR‐495‐3p and together regulate the proliferation and invasion of gastric cancer

Abstract

High expression of special AT‐rich‐binding protein 1 (SATB1) correlates with the advanced TNM stage and short overall and recurrence‐free survival of gastric cancer (GC). A bioinformatic analysis revealed that SATB1 3′‐untranslated region (3′‐UTR) and long noncoding RNA UCA1 (lncRNA‐UCA1) might competitively bind to microRNA‐495‐3p (miR‐495‐3p). Interestingly, lncRNA‐UCA1 is also an important contributor to GC. The current study aimed to demonstrate the potential interaction among SATB1/miR‐495‐3p/lncRNA‐UCA1 network and their effects on GC proliferation and invasion. The expression in GC and paracancerous normal tissues were assessed using real‐time polymerase chain reaction and Western blot analysis. Luciferase reporter, RNA pull‐down, and transfection assays were performed to determine the interaction among SATB1/miR‐495‐3p/lncRNA‐UCA1 network in GC cells. GC proliferation and invasion were evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, transwell invasion, and colony formation assays. Results showed higher expression of SATB1 and lncRNA‐UCA1 but lower miR‐495‐3p expression in GC than in the normal tissues. In luciferase reporter assay, miR‐495‐3p bound to three seed sequences in SATB1 3′‐UTR but only one in lncRNA‐UCA1. SATB1 knockdown increased the combination of miR‐495‐3p with lncRNA‐UCA1 but decreased lncRNA‐UCA1 expression. Decreased lncRNA‐UCA1 was also observed with the mimics increased miR‐495‐3p. These data suggested that SATB1 3′‐UTR functions as a competing endogenous RNA of miR‐495‐3p and positively regulates lncRNA‐UCA1. LncRNA‐UCA1 knockdown only decreased SATB1 expression in MKN‐45 cells but not in BGC‐823 cells, which suggested that the regulatory effect of lncRNA‐UCA1 on SATB1 by sponging miR‐495‐3p is cell‐dependent. This study further identified that SATB1/miR‐495‐3p/lncRNA‐UCA1 network is implicated in GC proliferation and invasion. The current study firstly revealed that SATB1 interacts with miR‐495‐3p/lncRNA‐UCA1 network, whereby enhancing GC proliferation and invasion.

Crosstalk between the lncRNA UCA1 and microRNAs in cancer

“…Thus, there is an interaction between HIF-1a and UCA1 under hypoxic conditions. SATB1 depletion increases the promoter activity of UCA1 [30]. SATB1 depletion increases the promoter activity of UCA1 [30].…”

“…Similarly, UCA1 enhanced the invasion of GC by directly interacting with miR-203 or miR-7-5p, increasing the release of miR-203-targeted transcripts zinc finger E-box-binding homeobox2 (ZEB2) or miR-7-5p-targeted epidermal growth factor receptor (EGFR), respectively [64,65]. Moreover, UCA1 also could promote the proliferation and invasion of GC through sponging miR-495-3p [30]. SATB1 is a target of miR-495-3p and positively correlated with the advanced tumor node metastasis stage of GC [66].…”

“…In addition, UCA1 is regulated by other transcription factors such as special AT-rich sequence binding protein 1 (SATB1), which binds to the upstream region of UCA1 to block its transcription [29]. SATB1 depletion increases the promoter activity of UCA1 [30]. Moreover, the transforming growth factor-b (TGF-b) pathway could induce the expression of UCA1 by recruiting a transcriptional complex composed of TAZ, yes-associated protein (YAP), TEAD and SMAD2/3 in breast cancer cells [31,32].…”

miR‐449c‐5p availability is antagonized by circ‐NOTCH1 for MYC‐induced NOTCH1 upregulation as well as tumor metastasis and stemness in gastric cancer

“…**P < .01, ***P < .001 with long non-coding RNAs (lncRNAs), mRNAs or circRNAs. 19,21,22 miR-449c-5p functions essentially in hepatocellular carcinoma. 23 miR-449c-5p represses osteogenic differentiation of VICs by Smad4-modulated pathway.…”

Long non-coding RNA NORAD exhaustion represses prostate cancer progression through inhibiting TRIP13 expression via competitively binding to miR-495-3p

“…MiR-495-3p served as a suppressor in gastric carcinogenesis via modulating multiple epigenetic modifiers [ 19 ]. Also, the lncRNA UCA1/miR-495-3p/SATB1 axis was related to cell invasion and proliferation in gastric cancer [ 20 ]. However, whether miR-495-3p can be regulated by NORAD has not been reported.…”