Non-coding RNA Urothelial Carcinoma Research Articles

LncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer.

Long noncoding RNA urothelial carcinoma associated 1(UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real-time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull-down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain- and loss-of-function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.

LncRNA UCA1 could regulate the progression of neuropathic pain by regulating miR-135a-5p

BackgroundNeuropathic pain (NPP) is known as a common neurological disease with high incidence rate. The present work focused on the roles of long non-coding RNA urothelial carcinoma antigen 1(LncRNA UCA1) in NPP and the possible underlying mechanism. MethodsNPP rat model has been established and the levels of UCA1 NPP as well as the group has been determined by RT-PCR method. Next, NPP rats were treated by UCA1 over-expression plasmid and the behaviors, as well as expression of inflammatory cytokines have been examined. Furthermore, target miRNA of UCA1, miR-135a-5p, has been predicted by bioinformatic method, and further verified with the dual-luciferase reporter assay. Finally, the effects of UCA1/ miR-135a-5p axis have been further evaluated. ResultsExpressions of UCA1 were markedly decreased and miR-135a-5p were significantly increased in NPP rats in comparison with the control rats. Over-expression of UCA1 alleviated the inflammatory condition in NPP model by decreasing expression of inflammatory cytokines. miR-135a-5p was confirmed to be a target microRNA of UCA1, and UCA1 may regulate the progress of NPP via targeting miR-135a-5p. ConclusionUCA1 could regulate NPP via affecting miR-135a-5p expression.

Elevated lncRNA-UCA1 upregulates EZH2 to promote inflammatory response in sepsis-induced pneumonia via inhibiting HOXA1.

Sepsis is characterized by a dysregulated inflammatory response. We aimed to explore the role of the long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1)/enhancer of zeste homolog 2 (EZH2)/homeobox A1 (HOXA1) axis in sepsis-induced pneumonia. The sepsis rat models and RLE-6TN cellular sepsis-induced pneumonia models were established using ligation and puncture (CLP) and lipopolysaccharide (LPS). The expression of UCA1, EZH2, and HOXA1 in rat lung tissues and RLE-6TN cells was detected. Then, the CLP rats were respectively treated with lentivirus to upregulate or downregulate the expression of UCA1 and EZH2 to measure their roles in the pathology, apoptosis, inflammation and phosphorylated NF-κB p65(p-p65) levels in CLP rat lung tissues. UCA1 and EZH2 expression was upregulated or downregulated in LPS-induced RLE-6TN cells to explore their effects on cell viability, apoptosis, inflammation and p-p65 levels. The interactions among UCA1, EZH2, and HOXA1 were identified. UCA1 and EZH2 were upregulated whereas HOXA1 was downregulated in CLP rat lung tissues and LPS-induced RLE-6TN cells. Elevated UCA1 or increased EZH2 aggravated pathology and promoted apoptosis, inflammation and phosphorylated NF-κB p-65 levels in CLP rat lung tissues, and inhibited viability while facilitated apoptosis, inflammation and phosphorylated NF-κB p-65 levels in LPS-induced RLE-6TN cells. Silenced EZH2 reversed the effects of UCA1 elevation on sepsis-induced pneumonia. UCA1 suppressed HOXA1 expression through physically interacting with EZH2. UCA1 overexpression upregulates EZH2 to repress HOXA1 expression, thus aggravating the progression of sepsis-induced pneumonia, which could be alleviated by EZH2 inhibition.

Overexpression of long non-coding RNA urothelial carcinoma associated 1 causes paclitaxel (Taxol) resistance in colorectal cancer cells by promoting glycolysis

Some colorectal cancer patients show resistance to conventional chemotherapeutic agents including Taxol. This study investigated the roles of lncRNA urothelial carcinoma-associated 1 (UCA1) in the modulation of Taxol resistance in human colorectal cancer cells. According to our results, UCA1 was significantly upregulated in colon cancer cell lines/tissues. Construction of the UCA1 overexpression vector revealed that high UCA1 expression was responsible for Taxol resistance and that Taxol can induce UCA1 expression. Importantly, Taxol-resistant cells had a higher glycolysis rate and upregulated expression of the key glycolysis enzymes hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA) than Taxol-sensitive cells. Further research demonstrated that UCA1 could directly regulate glycolysis by regulating HK2 and LDHA expression, which contributes to Taxol resistance. UCA1 is a potential target to overcome chemoresistance in colorectal cancer. We report the modulation of UCA-1-regulated glycolysis as a novel anticancer strategy along with the novel role of UCA1 in Taxol resistance.

Long noncoding RNA UCA1 from hypoxia-conditioned hMSC-derived exosomes: a novel molecular target for cardioprotection through miR-873-5p/XIAP axis

Exosomes (Exo) secreted from mesenchymal stem cells (hMSCs) are protective against myocardial injury. The purpose of the study was to investigate the role and mechanisms by which exosomes promote cardiomyocyte survival and function following myocardial infarction (MI). hMSCs were cultured under hypoxic and normoxic conditions. Hypoxia-conditioned hMSC-derived exosomes (Hypo-Exo) and normoxic-conditioned hMSC-derived exosomes (Nor-Exo) were collected and intramyocardially injected into rats with MI. The therapeutic effects of Hypo-Exo and Nor-Exo were evaluated after 4 weeks. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of candidate long noncoding RNA urothelial carcinoma associated 1 (lncRNA-UCA1) in Nor-Exo and Hypo-Exo. Intramyocardial injection of lncRNA-UCA1-knockdown-Hypo-Exo in a rat model of MI was then performed and the cardiac function was characterized. The target and downstream of the molecular mechanism lncRNA-UCA1 was disclosed by luciferase reporter assays and western blot. Circulating exosomal lncRNA-UCA1 level in AMI patients and healthy volunteers was assessed. We found that (1) hMSC exosomal (from hypoxic and normoxic conditions) cardioprotection in vitro and in vivo correlated with the presence of encapsulated lncRNA-UCA1 in exosomes; (2) lncRNA-UCA1 targeted miR-873 via sponging, reducing the latter’s suppressive effects on its target XIAP, and this translated into AMPK phosphorylation and increased level of the antiapoptotic protein BCL2; and (3) plasma derived from patients with AMI contained exosomes enriched with the lncRNA-UCA1, unlike that from normal subjects. This study demonstrates that Hypo-Exo lncRNA-UCA1 plays a cardioprotective role via the miR-873-5p/XIAP axis and circulating exosomal lncRNA-UCA1 may be a promising novel biomarker for the diagnosis of AMI.

LncRNA UCA1 Contributes to 5-Fluorouracil Resistance of Colorectal Cancer Cells Through miR-23b-3p/ZNF281 Axis.

PurposeThe chemoresistance of 5-fluorouracil (5-FU) limited the application of chemotherapy in colorectal cancer (CRC) treatment. Herein, we aimed to uncover the potential mechanism behind the 5-FU resistance of CRC cells.MethodsThe abundance of long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1), microRNA-23b-3p (miR-23b-3p) and zinc finger protein 281 (ZNF281) was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cells. Western blot was conducted to examine autophagy-related proteins, apoptosis-associated proteins and ZNF281 in CRC tissues and cells. Cell counting kit-8 (CCK8) assay was performed to detect the viability and inhibitory concentration 50% (IC50) value of 5-FU of CRC cells. The apoptosis of CRC cells was measured by flow cytometry. The binding sites between miR-23b-3p and UCA1 or ZNF281 were predicted by miRcode and Starbase software, respectively, and the combination was confirmed by dual-luciferase reporter assay and RIP assay. Murine xenograft model was established to verify the role of UCA1 on the 5-FU resistance of CRC in vivo.ResultsThe 5-FU resistance of CRC was positively related to the level of UCA1 and autophagy. UCA1 accelerated the 5-FU resistance of CRC cells through facilitating autophagy and suppressing apoptosis. MiR-23b-3p was a target of UCA1 in 293T and CRC cells. The knockdown of miR-23b-3p reversed the inhibitory effects of UCA1 interference on the 5-FU resistance and autophagy and the promoting impact on the apoptosis of CRC cells. ZNF281 could bind to miR-23b-3p in 293T cells. MiR-23b-3p elevated the 5-FU sensitivity through down-regulating ZNF281 in CRC cells. UCA1 interference enhanced the 5-FU sensitivity of CRC through miR-23b-3p/ZNF281 axis in vivo.ConclusionUCA1 mediated 5-FU resistance of CRC cells through facilitating autophagy and inhibiting apoptosis via miR-23b-3p/ZNF281 axis in vivo and in vitro.

Long Noncoding RNA UCA1 Facilitates Endometrial Cancer Development by Regulating KLF5 and RXFP1 Gene Expressions.

Objective: Long noncoding RNA urothelial carcinoma associated 1 (UCA1) was found to facilitate endometrial cancer cell metastasis, and high UCA1 expression predicted endometrial cancer development and patients' worsened outcomes. This research aimed to investigate the cancer promoting role and mechanism of UCA1 in endometrial cancer. Materials and Methods: Around 64 endometrioid adenocarcinoma patients' tissue specimens were analyzed by qRT-PCR. Primary endometrial cancer cell culture was established in vitro. UCA1 overexpression or knockdown was executed by adenoviral transduction. Cell proliferation, apoptosis, colony formation, transwell invasion, and epithelia-to-mesenchymal transition of primary endometrial cancer cells were assessed. Interactions among UCA1, microRNAs (miRNAs), and mRNAs were investigated by luciferase reporter assay and argonaute 2 (AGO2)-RNA immunoprecipitation. Nude mouse xenograft assay was used to explore the role of UCA1 in endometrial cancer in vivo. Results: UCA1 was significantly upregulated in endometrial cancer tissues compared to normal tissues. High expression of UCA1 associated with endometrial cancer progression and patients' decreased survival. Overexpressing UCA1 significantly increased the malignancy of primary endometrial cancer cells in vitro, while UCA1 knockdown showed opposite effect. Kruppel-like factor 5 (KLF5) and relaxin like family peptide receptor 1 (RXFP1) were found as two UCA1 co-expressing genes in endometrial cancer. UCA1 increased the malignancy of endometrial cells partially through KLF5, and it increased the relaxin 2-induced endometrial cancer cell metastasis through RXFP1. UCA1 reduced the si-RNA-induced silencing of KLF5 and RXFP1 genes in endometrial cancer cells. MiR-143-3p and miR-1-3p were found to interact with both UCA1 and KLF5 mRNA. In addition, knockdown of UCA1 suppressed tumor growth in endometrial cancer in vivo. Conclusion: UCA1 might facilitate endometrial cancer development by upregulating KLF5 and RXFP1 gene expression by sponging miR-143-3p and miR-1-3p.

Downregulated lncRNA UCA1 accelerates proliferation and migration of vascular smooth muscle cells by epigenetic regulation of MMP9.

Function of long non-coding RNA urothelial carcinoma antigen 1 (lncRNA UCA1) in regulating the proliferative and migratory abilities of vascular smooth muscle cells (VSMCs) by mediating matrix metalloproteinase-9 (MMP9) level were elucidated. After treatment with different concentrations of ox-LDL for different time points, lncRNA UCA1 level in VSMCs was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular distribution of UCA1 was analyzed. Proliferative and migratory abilities of VSMCs transfected with pcDNA-UCA1 were assessed. Protein level of MMP9 in HA-VSMCs treated with different concentrations of ox-LDL for different time points was also determined. The potential interaction between UCA1 and enhancer of zeste homolog 2 (EZH2) was identified by RNA immunoprecipitation (RIP) assay. Recruitment ability of EZH2 to MMP9 promoter region influenced by UCA1 was determined by Chromatin immunoprecipitation (ChIP) assay. Finally, the potential function of MMP9 in UCA1-mediated cellular behavior of VSMCs was explored. UCA1 was time-dependently and dose-dependently upregulated in VSMCs by ox-LDL treatment. Proliferative and migratory abilities of VSMCs were enhanced by treatment of 100 mg/l ox-LDL for 48 h, which were further reduced after transfection of pcDNA-UCA1. Subcellular distribution analysis showed that UCA1 was mainly distributed in the nucleus. Protein level of MMP9 was gradually elevated with the treatment of increased concentrations of ox-LDL in VSMCs. Its level was downregulated by transfection of pcDNA-UCA1 in VSMCs. The interaction between UCA1 and EZH2 was confirmed by RIP assay. Transfection of pcDNA-UCA1 stimulated the binding of EZH2 on MMP9 promoter region. Finally, overexpression of MMP9 reversed the decreased proliferative and migratory abilities in ox-LDL-treated VSMCs overexpressing UCA1. Downregulated UCA1 accelerates VSMCs to proliferate and migrate through negatively regulating MMP9 level.

Long-chain non-coding RNA UCA1 inhibits renal tubular epithelial cell apoptosis by targeting microRNA-206 in diabetic nephropathy

In this study, the inhibitory effect of long-chain non-coding RNA urothelial carcinoma associated 1 (UCA1) on renal tubular epithelial cell apoptosis by targeting microRNA (miRNA)-206 in diabetic nephropathy (DN) was investigated through DN rat model. The results showed that UCA1 expression was significantly reduced in diabetic renal tubular epithelial tissues and HG-induced HK-2 cells. UCA1 significantly inhibited HG-induced apoptosis and inflammation of renal tubular epithelial cells in HK-2 cells. In addition, UCA1 can directly act as an anti-pro-cytokine by inhibiting the expression of miR-206, and finally inhibit the apoptosis and inflammation of renal tubular epithelial cells. We conclude that UCA1 inhibits renal tubular epithelial cell apoptosis by targeting miRNA-206 in DN and can be used as a potential therapeutic target for DN.

Long Noncoding RNA UCA1 Overexpression Is Associated with Poor Prognosis in Digestive System Malignancies: A Meta-analysis.

Long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) has been reported to be highly expressed in many kinds of cancers. This meta-analysis summarized its potential prognostic value in digestive system malignancies. A meta-analysis was performed through a comprehensive search in PubMed, EMBASE, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI) for suitable articles on the prognostic impact of UCA1 in digestive system malignancies from inception to June 27, 2019. Pooled hazard ratios (HRs) with 95% confidence interval (95%CI) were calculated to summarize the effect. Sixteen studies were included in the study, with a total of 1504 patients. A significant association was observed between UCA1 abundance and poor overall survival (OS), and shorter disease-free survival (DFS) for patients with digestive system malignancies, with pooled HR of 2.07 (95%CI: 1.74-2.47), and of 2.50 (95%CI: 1.62-3.86). Subgroup analysis and sensitivity analysis suggested the reliability of our findings. It is suggested that UCA1 abundance may serve as a reliable predictive factor for poor prognosis in patients with digestive system malignancies.

Long Noncoding RNA UCA1 Accelerates Nasopharyngeal Carcinoma Cell Progression By Modulating miR-124-3p/ITGB1 Axis.

BackgroundNasopharyngeal carcinoma (NPC) is a common malignant cancer that is distributed particularly in Southeastern Asia. Previous studies have manifested that long noncoding RNA urothelial carcinoma associated 1 (UCA1) was involved in NPC tumorigenesis and metastasis. However, the biological mechanism of UCA1 for NPC cell progression requires further investigation.MethodsThe expression levels of UCA1, miR-124-3p, integrin beta-1 (ITGB1) were detected by qRT-PCR. Protein expression of ITGB1 was determined by Western blot assay. Cell proliferation, migration and invasion were evaluated by CCK8 and transwell assay, respectively. The interaction between miR-124-3p and UCA1 or ITGB1 was determined by luciferase reporter system, RIP and RNA pull-down assay. Mice model was established by subcutaneously injecting SUNE1 cells stably transfected with sh-UCA1 and sh-NC.ResultsThe expression of UCA1 was up-regulated in NPC tissues and cells. However, UCA1 knockdown hindered NPC cell growth, migration and invasion. In addition, the interaction between miR-124-3p and UCA1 or ITGB1 was confirmed by luciferase reporter system, RIP and RNA pull-down assay. Besides, miR-124-3p inhibitor abrogated UCA1 silencing-mediated suppression on cell progression in NPC. Moreover, UCA1 accelerated NPC cell progression through modulating ITGB1 via sponging miR-124-3p. In vivo experiments revealed the interference of UCA1-inhibited tumor growth by regulating miR-124-3p/ITGB1 axis.ConclusionUCA1 acts as an oncogene to promote NPC cell proliferation by up-regulating ITGB1 through suppressing miR-124-3p in vitro and in vivo, providing a potential target for NPC diagnosis and treatment.

Long non-coding RNA UCA1 relieves cardiomyocytes H9c2 injury aroused by oxygen-glucose deprivation via declining miR-122

Background Many lncRNAs have been recognized as critical regulatory factors in acute myocardial infarction (AMI). Herein, we further tested the influence of long non-coding RNA urothelial carcinoma associated 1 (UCA1) on cardiomyocytes injury in AMI, along with the role of microRNA-122 (miR-122) in this influence. Methods Cardiomyocytes H9c2 was subjected to oxygen-glucose deprivation (OGD) stimulation. Cell viability and apoptosis were assessed. The UCA1 and miR-122 expressions were measured by qRT-PCR. Plasmids and miRNAs transfection were utilized to elevate UCA1 and miR-122 expressions. Subsequently, the influences of UCA1 and/or miR-122 overexpression on OGD-aroused H9c2 cell viability inhibition and apoptosis were probed. The AKT/mTOR and JNK/p38MAPK pathways in cells were analyzed. Results OGD aroused H9c2 cell injury by suppressing cell viability and elevating cell apoptosis. Followed by OGD stimulation, the UCA1 expression was lowered in H9c2 cells. Overexpression of UCA1 weakened H9c2 cell injury aroused by OGD and declined miR-122 expression. Moreover, miR-122 attended to the influence of UCA1 overexpression on OGD-aroused H9c2 cell injury. Overexpression of UCA1 weakened OGD-aroused AKT/mTOR pathway inactivation and JNK/p38MAPK pathway activation by declining miR-122. Conclusion UCA1-relieved OGD-aroused H9c2 cell injury might be achieved via declining miR-122 and then promoting AKT/mTOR pathway and suppressing JNK/p38MAPK pathway.

Function of Long Noncoding RNA UCA1 on Gastric Cancer Cells and its Clinicopathological Significance in Plasma.

Diagnosis and treatment of gastric cancer (GC) at early stages is challenging, causing great difficulties to patients. Long noncoding RNAs (lncRNAs) may serve both as novel molecular markers and therapeutic targets in diagnosis and prognosis of cancers. This study aimed to investigate the function of long non-coding RNA Urothelial Carcinoma Associated 1 (UCA1) on GC cells and evaluate its diagnostic value in GC. In total, 90 patients with GC and 43 healthy individuals were recruited for the study. Venous blood samples from 40 of the 90 GC patients who underwent surgery were collected before and one week after the surgery. Thirty GC and matched normal tissues were sampled from patients who had undergone surgical resection. The plasma level of UCA1 was quantified using RT-qPCR. In situ hybridization was carried out on formaldehyde-fixed tissue sections from GC patients to detect UCA1. Cell migration assay, cell proliferation assay, and flow cytometry analysis were carried out to study the effect of UCA1 on GC development in vitro. RT-PCR results showed that the expression levels of UCA1 in GC tissues were significantly higher compared to those in adjacent normal specimens. Down-regulation of UCA1 inhibited the proliferation, migration, and apoptosis of GC cells. In GC patients, plasma expression of UCA1 was significantly up-regulated compared to that in healthy controls (1.417 ± 0.106 vs. 0.223 ± 0.030, p < 0.0001). Plasma UCA1 was significantly correlated with tumor differentiation (p < 0.05), T stage (p < 0.001) and lymph node metastasis (p < 0.001). Plasma UCA1 expression (AUC = 0.883) in post-surgery samples was significantly decreased compared to the expression level of pre-surgery patients (1.403 ± 1.329 versus 0.712 ± 0.944, p < 0.01). UCA1 promoted proliferation, migration and apoptosis of GC cells and was significantly up-regulated in GC plasma, indicating poor tumor prognosis.

Synergistic Antitumor Effect on Bladder Cancer by Rational Combination of Programmed Cell Death 1 Blockade and CRISPR-Cas9-Mediated Long Non-Coding RNA Urothelial Carcinoma Associated 1 Knockout.

Targeted therapy produces objective responses in bladder cancer patients, although the responses can be short. Meanwhile, response rates to immune therapy are lower, but the effects are more durable. Based on these findings, it was hypothesized that urothelial carcinoma associated 1 (UCA1)-targeted therapy could synergize with programmed cell death 1 (PD-1) blockade to enhance antitumor activity. To test this hypothesis, the effects of CRISPR-Cas9 targeting of UCA1 and PD-1 were assessed in vitro and in vivo. It was found that gRNA/cas9-targeted UCA1 induced apoptosis of 5637 bladder cancer cells, whereas PD-1 gene knockout could be achieved by electroporation of gRNA/cas9 targeting PD-1, as detected by polymerase chain reaction. In 5637 cell-xenografted humanized SCID mice, stimulation with CRISPR-Cas9 systems, immune phenotypes, and cytokine expression of human dendritic cells (DCs) was detected by flow cytometry, and polymerase chain reaction, respectively. The results of these assays suggested that the gRNA/cas9 treatment upregulated expression of CD80, CD83, and CD86 and significantly increased interleukin (IL)-6, IL-12, and IL-23 and tumor necrosis factor alpha mRNA levels. Co-administration of anti-PD-1 and anti-UCA1 treatment suppressed tumor growth and markedly improved survival of 5637 xenografted mice. Additionally, the combination treatment increased interferon gamma production by T cells that subsequently enhanced the expression of Th1-associated immune-stimulating genes to reduce transcription of regulatory/suppressive immune genes and reshape the tumor microenvironment from an immunosuppressive to a stimulatory state. Finally, anti-UCA1 treatment was shown to induce interferon gamma-dependent programmed cell death ligand 1 expression within 5637 xenograft tumors in vivo. Together, these results demonstrate potent synergistic effects of a combination therapy using LncRNA UCA1-targeted therapy and immune checkpoint blockade of PD-1, thus supporting the translational potential of this combination strategy for clinical treatment of bladder cancer.

Knockdown of long noncoding RNA urothelial carcinoma associated 1 inhibits colorectal cancer cell proliferation and promotes apoptosis via modulating autophagy.

Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been implicated in the growth and metastasis of colorectal cancer (CRC), and autophagy contributes to tumorigenesis and cancer cell survival. However, the regulatory role of UCA1 in CRC cell viability by modulating autophagy remains unclear. In the present study, a significant positive correlation was observed between UCA1 and microtubule-associated protein 1 light chain 3 (LC3) levels, and the elevated UCA1 was negatively correlated with the PKB/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in 293T cells. Downregulation of UCA1 inhibited autophagy activation and cell proliferation, whereas the apoptosis was increased and the cell cycle was arrested in G2 stage. The next results showed that UCA1 was markedly upregulated in Caco-2 cells. Knockdown of UCA1 significantly decreased the LC3-II and autophagy-related gene 5 (ATG5) protein levels and resulted in an increase in p62 expression. Conversely, the autophagy activator rapamycin (RAPA) reversed the effects. Furthermore, downregulated UCA1 decreased Caco-2 cells population in the G1 phase and increased the cells number in G2 phage. The cell proliferation was inhibited, and apoptosis rate was promoted. More important, RAPA could also abrogate the changes induced by knockdown of UCA1. Collectively, these data demonstrated that downregulated UCA1 induced autophagy inhibition, resulting in suppressing cell proliferation and promoting apoptosis, which suggested that UCA1 might serve as a potential new oncogene to regulate CRC cells viability by modulating autophagy.

UCA1 promotes papillary thyroid carcinoma development by stimulating cell proliferation via Wnt pathway.

To explore whether lncRNA UCA1 (long non-coding RNA urothelial carcinoma associated 1) could promote the development of papillary thyroid carcinoma (PTC) via Wnt pathway and its underlying mechanism. UCA1 expression in PTC tissues, paracancerous tissues, and thyroid cancer cells were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). UCA1 lentivirus was then constructed for the following in vitro experiments. Proliferative ability of MTC and SW579 cells was detected by cell counting kit-8 (CCK-8) and colony formation assay. Cell apoptosis after altering UCA1 expression in MTC and SW579 cells was detected by flow cytometry and Western blot. Invasive ability of MTC and SW579 cells was detected by transwell and wound healing assay. Finally, protein expressions of Wnt pathway-related genes were detected by Western blot. UCA1 was overexpressed in PTC tissues and thyroid cancer cells. UCA1 expression was positively correlated to tumor size, tumor stage, and metastasis of PTC. Overexpressed UCA1 promoted proliferation and invasion, whereas inhibited apoptosis of thyroid cancer cells via Wnt pathway. Overexpressed UCA1 promotes PTC development by stimulating proliferation, migration, and anti-apoptosis of thyroid cancer cells via activating Wnt pathway.

Knockdown of long noncoding RNA urothelial carcinoma-associated 1 inhibits cell viability, migration, and invasion by regulating microRNA-182 in gastric carcinoma.

Long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been reported to be a vital mediator in various cancers. But, in terms of gastric cancer (GC), the effects of UCA1 on GC cell proliferation, migration, invasion, and apoptosis remain unclear. This study aimed to uncover the potential regulatory mechanism of UCA1 in GC cells. The expression level of UCA1 was first examined in the five different cell lines of HEK293, CCL-153, HUVEC, SUN-216, and SGC-7901 using a reverse-transcriptase quantitative polymerase chain reaction. Then, the vectors of short hairpin UCA1, the microRNA-182 (miR-182) mimic/inhibitor, and the pEX-tissue inhibitor of metalloproteinases 2 (TIMP2)/small interfering TIMP2 were transfected into SUN-216 and SGC-7901 cells to alter UCA1, miR-182, and TIMP2 expression. To investigate the biological functions, cell viability, migration, invasion, and apoptosis were examined by Cell Counting Kit-8, Transwell, and flow cytometry. The key factors of apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK3β) and nuclear factor κB (NF-κB) signal pathways were determined by Western blot analysis. UCA1 was upregulated in SUN-216 and SGC-7901 cells than in the other three cell lines of HEK293, CCL-153, and HUVEC. Knockdown of UCA1 significantly suppressed cell viability, migration, and invasion, and promoted apoptosis by regulating B-cell lymphoma 2, Bax, and cleaved-caspase-3/9 expressions. However, miR-182 overexpression markedly reversed the regulatory effect of UCA1 knockdown on SUN-216 and SGC-7901 cells. TIMP2 was a direct target gene of miR-182, and TIMP2 overexpression exhibited the same effect of UCA1 knockdown on cell viability, migration, invasion, and apoptosis. Besides, miR-182 activated PI3K/AKT/GSK3β and NF-κB signal pathways by regulation of TIMP2. Knockdown of UCA1 exerts an anticancer effect on GC cells by regulating miR-182.

LncRNA UCA1 sponges miR-204-5p to promote migration, invasion and epithelial-mesenchymal transition of glioma cells via upregulation of ZEB1

Long non-coding RNA urothelial carcinoma associated 1 (lncRNA UCA1) promotes cancer progression and enhances chemoresistance through miR-204-5p in a few cancers. However, no studies have investigated whether UCA1 regulates glioma metastasis through miR-204-5p and its target. In the present study, cell migration, invasion and epithelial-mesenchymal transition (EMT) were evaluated in glioma cells overexpressing UCA1. The relationships among UCA1, miR-204-5p and ZEB1 were examined by real-time PCR, western blotting and dual-luciferase reporter assays. The effect of UCA1 knockdown on xenograft tumor growth was investigated. The levels of miR-204-5p, fibronectin, COL5 A1 and ZEB1 in tumor tissues were also determined. The results showed that UCA1 overexpression promoted cell migration, invasion and EMT. UCA1 interacted with miR-204-5p and decreased its level. ZEB1 was identified as a direct target of miR-204-5p and miR-204-5p negatively regulated ZEB1 expression. Moreover, UCA1 sponged miR-204-5p and partially rescued the inhibitory effect of miR-204-5p on ZEB1. In our in vivo studies, UCA1 knockdown reduced tumor volume and tumor weight. In addition, the levels of fibronectin, COL5 A1 and ZEB1 were decreased, while miR-204-5p level was increased. The present study provides the first evidence that UCA1 promotes glioma metastasis through the miR-204-5p/ZEB1 axis, contributing to the understanding of the pathogenesis of glioma.

Article removed: Long Non-Coding RNA Urothelial Carcinoma Associated 1 Promotes Proliferation, Migration and Invasion of Osteosarcoma Cells by Regulating microRNA-182

Previous studies demonstrated the oncogenic roles of lncRNA UCA1 in osteosarcoma. This study aimed to explore the internal molecular mechanism of UCA1 on promoting osteosarcoma cell proliferation, migration and invasion. qRT-PCR was conducted to measure the expression levels of UCA1, miR-182 and TIMP2. Cell transfection was used to change the expression levels of UCA1, miR-182 and TIMP2. Cell viability, migration, invasion and apoptosis were measured using CCK-8 assay, two-chamber migration (invasion) assay and Guava Nexin assay, respectively. The associations between UCA1, miR-182 and iASPP were analyzed by dual luciferase activity assay. The protein expression levels of key factors involved in cell apoptosis, PI3K/AKT/GSK3β pathway and NF-κB pathway, as well as p53, Rb, RECQ family and iASPP were evaluated by western blotting. UCA1 was highly expressed in osteosarcoma MG63 and OS-732 cells. Knockdown of UCA1 inhibited OS-732 cell viability, migration and invasion, but promoted cell apoptosis. miR-182 was up-regulated in OS-732 cells after UCA1 knockdown and participated in the effects of UCA1 on OS-732 cells. TIMP2 was downstream factor of miR-182 and involved in the regulatory roles of miR-182 on OS-732 cell viability, migration, invasion, apoptosis, as well as PI3K/AKT/GSK3β and NF-κB pathways. UCA1 knockdown up-regulated p53, Rb and RECQL5 levels in OS-732 cells, while down-regulated the expression of iASPP. TGF-β or TNF-α treatment could enhance the expression of UCA1 in OS-732 cells. Our research verified that UCA1 exerted oncogenic roles in osteosarcoma cells by regulating miR-182 and TIMP2, as well as PI3K/AKT/GSK3β and NF-κB pathways.

Role of long non-coding RNA urothelial carcinoma associated antigen 1 as a competing endogenous RNA in the regulation of the initiation and progression of tumor

Long non-coding RNA urothelial carcinoma associated antigen 1 (UCA1) is highly expressed in multiple types of tumors, such as bladder cancer, breast cancer, colorectal cancer and so on. Recent studies show that UCA1 can interact with the microRNAs as a competing endogenous RNA (ceRNA), to indirectly regulate the expression of target genes, and then participates in the regulation of the initiation and progression of tumor. Therefore, using the mechanism of ceRNA to intervene the expression of UCA1 will provide new ideas for tumor treatment. Key words: Neoplasms; Long non-coding RNA; Urothelial carcinoma associated antigen 1; Competing endogenous RNA