Long non‐coding RNA urothelial cancer‐associated 1 promotes bladder cancer cell migration and invasion by way of the hsa‐miR‐145–ZEB1/2–FSCN1 pathway

Abstract

Numerous studies suggest that several long non‐coding RNAs (lncRNAs) play critical roles in bladder cancer development and progression. Long non‐coding RNA urothelial cancer‐associated 1 (lncRNA‐UCA1) is highly expressed in bladder cancer tissues and cells, and it has been shown to play an important role in regulating aggressive phenotypes of bladder cancer cells. However, little is known about the molecular mechanism of lncRNA‐UCA1‐mediated bladder cancer cell migration and invasion. Here, we show that overexpression of lncRNA‐UCA1 could induce EMT and increase the migratory and invasive abilities of bladder cancer cells. Mechanistically, lncRNA‐UCA1 induced EMT of bladder cancer cells by upregulating the expression levels of zinc finger E‐box binding homeobox 1 and 2 (ZEB1 and ZEB2), and regulated bladder cancer cell migration and invasion by tumor suppressive hsa‐miR‐145 and its target gene the actin‐binding protein fascin homologue 1 (FSCN1). Furthermore, we also observed a positive correlation between lncRNA‐UCA1 and ZEB1/2 expression, and a negative correlation between lncRNA‐UCA1 and hsa‐miR‐145 expression in bladder cancer specimens. Importantly, we found that lncRNA‐UCA1 repressed hsa‐miR‐145 expression to upregulate ZEB1/2, whereas the suppression of hsa‐miR‐145 could upregulate lncRNA‐UCA1 expression in bladder cancer cells. Moreover, the binding site for hsa‐miR‐145 within exons 2 and 3 of lncRNA‐UCA1 contributed to the reciprocal negative regulation of lncRNA‐UCA1 and hsa‐miR‐145. Taken together, our results identified that lncRNA‐UCA1 enhances bladder cancer cell migration and invasion in part through the hsa‐miR‐145/ZEB1/2/FSCN1 pathway. Therefore, lncRNA‐UCA1 might act as a promising therapeutic target for the invasion and metastasis of bladder cancer.

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR‑143/HMGB1 pathway

“…UCA1 is a sensitive and specific oncogenic lncRNA in bladder cancer (16). Consistent with previous observations that high UCA1 expression was involved in cell invasion in many cancers as well as bladder cancer (24,36,37), our results clearly showed that cells with stronger invasion capabil ity had higher UCA1 expression levels in bladder cancer cell lines in vitro. EMT is a well-characterized process that facilitates invasion and metastatic dissemination of human cancers (3,4).…”

“…To investigate the potential mechanism by which UCA1 regulates EMT in bladder cancer cells, we examined the effect of UCA1 on the expression of HMGB1, which is reported to be associated with the invasion ability of many types of human cancers including bladder cancer (24). qRT-PCR showed that HMGB1 mRNA expression was significantly (P<0.05) reduced by knockdown of UCA1 in T24 cells and increased by overexpression of UCA1 in RT4 cells (Fig.…”

“…Previous studies revealed that UCA1 expression is associated with enhanced invasion ability of bladder cancer cells (24,36,37). We first investigated the relationship between the expression of UCA1 and the invasion ability of five bladder cancer cell lines.…”

“…UCA1 is highly expressed in diverse cancer types, such as breast cancer (17), pancreatic cancer (18), gastric cancer (19), and colorectal cancer (20,21), suggesting that high expression of UCA1 might serve as a molecular marker for predicting metastasis and prognosis in these cancers (22). Several studies also demonstrated that upregulation of UCA1 is associated with EMT in breast cancer (23) and bladder cancer (24), but the underlying mechanism remains largely unknown.…”

Increased Expression of Long Non-Coding RNA BCAR4 Is Predictive of Poor Prognosis in Patients with Non-Small Cell Lung Cancer

“…In vitro study revealed that MVIH could promote cell proliferation and cell cycle, while inhibiting apoptosis of breast cancer cells. Xue et al (2016) reported that lncRNA urothelial cancer-associated 1 (UCA1) promoted the migration and invasion of bladder cancer cells via regulating the miR-145/ zinc finger E-box binding homeobox 1 and 2 (ZEB1 and ZEB2)/fascin homologue 1 (FSCN1) pathway. Therefore, understanding the exact roles of specific lncRNAs may contribute to the development of the diagnostics and therapeutics of human cancers.…”