Role Of Urothelial Cancer Associated 1 Research Articles

Knockdown of UCA1 restrains cell proliferation and metastasis of diffuse large B‑cell lymphoma by counteracting miR‑331‑3p expression

Long non-coding RNA urothelial cancer associated 1 (UCA1) has been reported to act as a carcinogen in bladder cancer, while its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. The present study was designed to explore the expression pattern and role of UCA1 in DLBCL. The expression pattern of UCA1 and microRNA (miR)-331-3p in DLBCL tissues and cell lines were detected by RT-qPCR. Dual luciferase reporter assay was performed to explore the relationship between UCA1 and miR-331-3p. Cell proliferation was explored by MTT assay. Cell migration and invasion abilities were assessed by Transwell assay. In the present study, it was revealed that the expression of UCA1 was significantly upregulated, while miR-331-3p was downregulated in DLBCL tissues and cell lines. Moreover, UCA1 was revealed to competitively bind with miR-331-3p in DLBCL. Functionally, knockdown of UCA1 was revealed to suppress cell proliferation, migration and invasion in DLBCL cells. Furthermore, upregulation of miR-331-3p prevented cell proliferation, migration and invasion in DLBC cells. In conclusion, the present findings firstly demonstrated that UCA1 silencing restrained DLBCL cell proliferation and metastases viability by suppressing miR-331-3p expression. It is suggested that UCA1 could be a possible medicinal target and biomarker for DLBCL.

Urothelial cancer associated 1 (UCA1) regulates trophoblast viability, proliferation, and migration via modulating the UCA1/miR-455/RUNX2 signaling pathway.

Spontaneous abortion (SA) is the spontaneous loss of a pregnancy before 20 gestational weeks. The causes of SA are still largely unknown. Long noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1) plays an important role in cellular progress. However, there is no report focusing on the role of UCA1 in SA. Here, we revealed that, compared with that in clinical samples from elective induced abortion, UCA1 expression was decreased in samples from SA patients as shown by qPCR method. The results demonstrated that UCA1 might be involved in the progress of SA. Then, we found that knockdown of UCA1 reduced cell viability and inhibited cell proliferation and migration of HTR-8/SVneo trophoblast cells as shown by CCK8, EdU, and Transwell methods. Furthermore, we demonstrated that UCA1 could act as a molecular sponge for miR-455 in HTR-8/SVneo cells as shown by luciferase reporter system method. In addition, miR-455 inhibited cell viability, cell proliferation and migration via regulating RUNX2 in HTR-8/SVneo cells. Ultimately, we illustrated that UCA1 plays its role via absorbing miR-455, thus promoting RUNX2 expression in HTR-8/SVneo cells. Collectively, this study first revealed the role and mechanism of UCA1 in the growth and migration of HTR-8/SVneo cells, indicating its potential as a diagnostic biomarker and therapeutic target for SA.

Abstract 514: Lncrna uca1 interacts directly with angiomotin to activate Hippo-YAP signaling in epithelial ovarian cancer

Abstract The long noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is upregulated in multiple cancers, including epithelial ovarian cancer (EOC). Our present study aims to dissect the functional and mechanistic role of UCA1 in EOC. We first explored the effects of stable UCA1 knockout mediated by CRISPR/Cas9 genome editing. The effects of UCA1 loss were more profound in vivo, as UCA1 knockout significantly impaired tumor growth in a mouse xenograft model. Pathways downstream of UCA1 were catalogued using reverse phase protein arrays, which revealed that YAP signaling is activated in UCA1-overexpressing ovarian cancer cells. To characterize the UCA1 interactome, in vivo RNA antisense purification (UCA1-iRAP) experiments were performed using a modified ChIRP and RAP protocol to isolate in vivo RNA direct interactomes based on hybridization of short (20 base) biotinylated probes at a physiologically relevant temperature (37°C). UCA1-iRAP was performed using an EOC cell model, and proteins extracted were profiled by mass spectrometry (MS). Altogether, 19 unique proteins were reproducibly detected by UCA1-iRAP-MS. Interestingly 16 of these UCA1-associated proteins were not previously known RNA-binding proteins. Integration of UCA1-iRAP-MS data with multilayered functional characteristics of UCA1 knockout/knockdown identified angiomotin (AMOT), a known Hippo-YAP signaling modulator, as potential interacting partner for UCA1. The interaction between UCA1 and AMOT was confirmed using both Western blotting for AMOT using UCA1-iRAP proteins, and RT-qPCR for UCA1 RNA after AMOT immunoprecipitation in 3 independent EOC cell lines. Knockdown experiments showed that AMOT is required for UCA1 to activate the expression of YAP target genes, including CYR61 and AXL. Our results indicate that UCA1 interacts directly with AMOT to promote cell growth by activation of Hippo-YAP signaling in EOC, and for the first time identify UCA1 as a novel upstream regulator of YAP signaling. Moreover, the optimized iRAP method we developed in this study can be readily applied to characterizing the protein, DNA, and RNA interactomes of noncoding or coding transcripts implicated other complex traits. Citation Format: Xianzhi Lin, Tassja J. Spindler, Simon A. Gayther, Kate Lawrenson. Lncrna uca1 interacts directly with angiomotin to activate Hippo-YAP signaling in epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 514.

Silencing of UCA1, a poor prognostic factor, inhibited the migration of endometrial cancer cell.

Endometrial cancer (EC) is a common female malignancy. Most patients were diagnosed at an early stage with a favorable prognosis. But more than 30% patients were high risk at III/IV stage with invading deep into the myometrium and progressively lead to local or extra pelvic metastasis. Urothelial cancer-associated 1 (UCA1) had been reported as the oncogenic long non-coding RNA in many tumors, but the role of UCA1 in EC is still unclear. QRT-PCR was used to analysis the level of UCA1 in the proliferative endometrium, primary EC tissue and lymph node metastasis tissue of EC. According to the QRT-PCR results of primary EC tissue, survival curves were made using the Kaplan-Meier method, and the log rank test was used to analyze the differences of clinicopathological characteristics and survival between the low expression and high expression group of UCA1 in EC patients. Moreover we knocked down the expression of UCA1 in EC cell lines HTB-111 and Ishikawa, and detected the migration and invasion ability of them with wound healing assay and transwell assay. The expression level of UCA1 using QRT-PCR method in lymph node metastasis tissue was the highest than that in the proliferative endometrium and primary EC tissues (1.15 ± 0.23, 3.23 ± 1.06 vs. 6.42 ± 1.46, P < 0.0001). For the primary EC tissue, the median fold change of UCA1 was used as a cutoff value. High UCA1 expression was observed to be closely correlated with lymph node metastasis (P = 0.008), distant metastasis (P = 0.003), grade (P = 0.009), advanced TNM stage (P = 0.031) and vessel invasive (P = 0.032). The 5-year overall survival rate in the high expression group was 41.7%, compared with 72.7% in the low expression group (P = 0.023). After silencing the UCA1, the migration and invasion ability of EC cell lines reduced significantly. Our findings provide the convincing evidence that the UCA1 plays an important role in the metastasis of EC and may serve as a novel molecular marker to predict the aggressive tumor progression and unfavorable prognosis of EC patients.