Expression Levels Of UCA1 Research Articles

LncRNA UCA1 promotes SOX12 expression in breast cancer by regulating m6A modification of miR-375 by METTL14 through DNA methylation.

Breast cancer, a multifactorial disease, represents one of the leading causes of cancer-related morbidity and mortality in women. This study set out to elucidate the underlying mechanism by which lncRNA UCA1 affects the m6A modification of miR-375 by mediating the DNA methylation of METTL14 and then altering SOX12 expression in breast cancer. First, the expression patterns of lncRNA UCA1, miR-375, and apoptosis-related factors were quantitated by means of RT-qPCR and western blot analysis. In addition, the proliferation, invasion, and apoptosis of cells were detected using CCK-8, Transwell, and flow cytometry, respectively. RIP was performed to further uncover the interaction of lncRNA UCA1 and DNA methyltransferases, and MSP was employed for METTL14 promoter region methylation. The DNA methyltransferase enrichment in the METTL14 promoter region was measured by ChIP. The targeting relationship between miR-375 and SOX12 was confirmed by bioinformatics analysis and dual-luciferase report assay. Lastly, the aforementioned mechanism was also verified using tumor xenograft in vivo. It was found the elevated lncRNA UCA1 expression levels serve as a risk factor of poor prognosis in breast cancer. Meanwhile, silencing lncRNA UCA1 could inhibit the proliferation and invasion, but promote apoptosis of breast cancer cells by reducing the DNA methylation of METTL14 and augmenting its expression. Furthermore, METTL14 was observed to mediate the low miR-375 expression through m6A modification, leading to increased SOX12 expression levels in breast cancer. Altogether, findings obtained in our study indicated that silencing lncRNA UCA1 curbed the progression of breast cancer through the METTL14-miR-375-SOX12 axis.

Hypoxic Tumor-Derived Exosomal Long Noncoding RNA UCA1 Promotes Angiogenesis via miR-96-5p/AMOTL2 in Pancreatic Cancer

The hypoxic microenvironment, an important feature of solid tumors, promotes tumor cells to release exosomes and enhances tumor angiogenesis. However, the detailed functions of hypoxic exosomes and the mechanisms underlying their effects in pancreatic cancer (PC) remain mysterious. Here, we observed that hypoxic exosomes derived from PC cells promoted cell migration and tube formation of human umbilical vein endothelial cells (HUVECs). The long noncoding RNA (lncRNA) UCA1, a key factor, was highly expressed in exosomes derived from hypoxic PC cells and could be transferred to HUVECs through the exosomes. In addition, the expression levels of UCA1 in exosomes derived from PC patients’ serum were higher than in healthy controls and were associated with poor survival of PC patients. Moreover, hypoxic exosomal UCA1 could promote angiogenesis and tumor growth both in vitro and in vivo. With respect to the functional mechanism, UCA1 acted as a sponge of microRNA (miR)-96-5p, relieving the repressive effects of miR-96-5p on the expression of its target gene AMOTL2. Collectively, these results indicate that hypoxic exosomal UCA1 could promote angiogenesis and tumor growth through the miR-96-5p/AMOTL2/ERK1/2 axis and therefore, serve as a novel target for PC treatment.

Effect of LncRNA UCA1 on radiosensitivity of lung cancer cells and its mechanism

Objective To evaluate the effect of long-chain non-coding RNA (LncRNA) UCA1 on the proliferation, apoptosis and radiosensitivity of lung cancer cell and to explore the underlying mechanism. Methods qRT-PCR was used to detect the expression of UCA1 and miR-513a-5p in lung cancer cell A549, H1299 and normal human lung cell HBE. The si-con group (transfected si-con), si-UCA1 group (transfected si-UCA1), miR-513a-5p group (transfected miR-513a-5p mimics), miR-NC group (transfected miR-NC), IR+ si-con group (transfected si-con, and irradiated), IR+ si-UCA1 group (transfected miR-NC and irradiated), IR+ miR-513a-5p group (transfected miR-513a-5p mimics and irradiated), IR+ miR-NC group (transfected miR-NC and irradiated), IR+ si-UCA1+ anti-miR-513a-5p group (co-transfected si-UCA1, anti-miR-513a-5p and irradiated) were transfected into the A549 and H1299 cells by liposome method, and then the cells in certain groups were subject to 4Gy irradiation. The cell proliferation of each group was detected by MTT assay. The sensitivity enhancement ratio was assessed by clone formation assay. The cell apoptosis of each group was detected by flow cytometry. The fluorescence activity of each group was detected by dual-fluorescein gene detection assay. Results Compared with human normal lung cell HBE, the expression levels of UCA1 were significantly up-regulated in the lung cancer cell A549 and H1299(both P<0.05), whereas those of miR-513a-5p were significantly down-regulated (both P<0.05). Inhibition of UCA1 and overexpression of miR-513a-5p significantly inhibited cell proliferation, promoted cell apoptosis and increased the sensitivity of radiation exposure of A549 and H1299(sensitivity enhancement ratio=1.897, 2.146 and 1.615, 1.872). miR-513a-5p could suppress the fluorescence activity of wild-type UCA1 cells, and UCA1 could negatively regulate the expression of miR-513a-5p. Inhibition of miR-513a-5p could reverse the enhancement effect of inhibiting UCA1 upon the radiosensitivity of lung cancer cells. Conclusions Inhibition of LncRNA UCA1 can enhance the sensitivity of radiation exposure to lung cancer cells. The mechanism may be related to the targeted inhibition of miR-513a-5p. Key words: UCA1 gene; miR-513a-5p gene; Radiosensitivity; Lung cancer cell line

Correlation between expression levels of lncRNA UCA1 and miR-18a with prognosis of hepatocellular cancer.

To uncover the prognostic potentials of long non-coding RNA (lncRNA) UCA1 and miR-18a in hepatocellular cancer (HCC). Expression levels of UCA1 and microRNA-18a (miR-18a) in HCC tissues and adjacent normal ones harvested from 55 HCC patients were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Clinical data of HCC patients were recorded, including pathological grading, tumor staging, intrahepatic metastasis, serum level of α-fetoprotein (AFP), tumor size, tumor number, recurrence, etc. Based on the median levels of UCA1 and miR-18a, enrolled HCC patients were classified into high-level and low-level group. Potential correlation between expression levels of UCA1 and miR-18a with survival of HCC patients was analyzed. The 4-year follow-up data of HCC patients were collected for analyzing factors that may influence prognosis in HCC patients by the Cox regression model. UCA1 was upregulated and miR-18a was downregulated in HCC tissues. HCC patients with stage III-IV, tumor size ≥5 cm or multiple tumors expressed high level of UCA1. Besides, HCC patients with stage I-II, non-intrahepatic metastasis or primarily diagnosed expressed a relatively low level of miR-18a. High-level UCA1 and low-level miR-18a predicted worse prognosis in HCC patients. Cox regression analysis revealed that tumor node metastasis (TNM) staging, intrahepatic metastases, postoperative recurrences, and UCA1 were risk factors for HCC, while miR-18a was the protective factor. LncRNA UCA1 is upregulated and miR-18a is downregulated in HCC tissues. High-level UCA1 and low-level miR-18a are closely linked to poor prognosis in HCC.

Circulating lncRNA UCA1 Promotes Malignancy of Colorectal Cancer via the miR-143/MYO6 Axis

Exosomes mediate cell-cell crosstalk in cancer progression by transferring a variety of biomolecules, including long noncoding RNAs (lncRNAs). Long non-coding RNA urothelial carcinoma-associated (UCA1) is a well-known lncRNA associated with the development and progression of various cancers, including colorectal cancer (CRC). However, the presence of UCA1 in exosomes and the roles and clinical values of exosomal UCA1 in CRC remain unknown. In this study, we systematically analyzed the expression profiles of exosomal lncRNAs in CRC patients using a high-throughput microarray assay. Then, we evaluated the UCA1 expression levels in a series of CRC tissues and the serum exosomes of CRC patients using quantitative real-time PCR. The roles of UCA1 on CRC in vitro and in vivo were investigated by MTT, colony formation, Transwell, quantitative real-time PCR, flow cytometry, and western blotting. The miRNA binding sites of UCA1 were predicted using the miRcode online database, and miR-143 was validated to target UCA1 by dual-luciferase activity assay and AGO2 RNA immunoprecipitation. Finally, the role of exosome-mediated UCA1 was further investigated by co-culturing with CRC cells. This study showed that UCA1 was upregulated in CRC tissues and functioned as an oncogene in CRC. Loss-of-function investigations showed that inhibition of UCA1 suppressed CRC cell proliferation and metastasis in vivo and in vitro. Mechanistically, UCA1 was identified as a miR-143 sponge. We also found that MYO6 was a direct target of miR-1205, which functioned as an oncogene in CRC. Moreover, UCA was also upregulated in the serum exosomes of CRC patients and could transfer UCA1 to CRC cells to increase their abilities of cell proliferation and migration. In conclusion, these data suggest that UCA1 could be an oncogene for CRC and may serve as a candidate target for new therapies in human CRC.

Sex-specific up-regulation of lncRNAs in peripheral blood of patients with schizophrenia

Schizophrenia as a common disabling psychiatric disorder has been associated with dysregulation of several genes and pathways among them are those being regulated by long non-coding RNAs (lncRNAs). Based on the acknowledged roles of lncRNAs in neurodevelopment, in the current study, we assessed expression of six lncRNAs namely HOXA-AS2, Linc-ROR, MALAT1, MEG3, SPRY4-IT1 and UCA1 in peripheral blood of 60 patients with schizophrenia and 60 healthy subjects. HOXA-AS2, Linc-ROR, MEG3, SPRY4-IT1 and UCA1 levels were significantly higher in total patients compared with total controls. However, when evaluating expression of genes in sex-based subgroups, the differences in the expression of these lncRNAs were significant only among females. Assessment of partial correlation between expression of lncRNAs and age of study participants after controlling the effect of sex, revealed significant correlations for HOXA-AS2, MALAT1 and UCA1 in both patients and controls. Besides, expressions of Linc-ROR and SPRY4-IT1 were correlated with age only in patients. Significant pairwise correlations were recognized between expression levels of lncRNAs in both patients with schizophrenia and controls. Based on the area under curve (AUC) values, SPRY4-IT1 had the best performance in differentiation of female patients with schizophrenia from female controls (AUC = 0.85, P < 0.0001). Combination of Linc-ROR, MEG3, SPRY4-IT1 and UCA1 expression levels could differentiate female patients with 95.2% sensitivity, 76.9% specificity and diagnostic power of 0.88 (P < 0.0001). The current study suggests the presence of a sex-based dysregulation of lncRNAs in patients with schizophrenia and their possible application as diagnostic biomarkers.

LncRNA UCA1 acts as a sponge of miR-204 to up-regulate CXCR4 expression and promote prostate cancer progression.

Prostate cancer (PCa) is a devastating malignant disease with a poor prognosis. The aim of current study is to investigate the role of lncRNA-urothelial carcinoma associated 1 (UCA1) in the progression of PCa. We evaluated the expression levels of UCA1 in a total of 16 benign prostatic hyperplasia tissues (BPH) and 40 PCa tissues, as well as PCa cells. The functional regulatory effects of UCA1 were investigated using a series of cell function approaches. Our data showed that UCA1 is frequently overexpressed in PCa tissues compared with BPH tissues (P<0.01). Moreover, the higher expression of UCA1 was observed in patients with Gleason score ≥8 (P<0.05). In consistent, we found the expression levels of UCA1 was higher in the PCa cell lines PC-3, LnCaP, and DU-145 than in the normal prostate epithelial cell line RWPE-1 (P<0.01). Functionally, we found knockdown of UCA1 in PC-3 significantly suppressed cell growth and invasion of PC-3, while overexpression of UCA1 in DU-145 cells promote cell growth and invasion. Mechanistically, UCA1 overexpression permitted activation of CXCR4 oncogenes through inhibition of miR-204 activity, as evidenced by the positive association of these two genes with UCA1 levels and inverse correlation with miR-204 expression in PCa tissues. Luciferase activity assay further confirmed the targetting relationship between UCA1 and miR-204, CXCR4, and miR-204. The up-regulation of UCA1 in PC-3 cells significantly impaired the inhibitory effect of miR-204 on CXCR4 expression. Taken together, our research revealed that UCA1 works as an oncogene by targetting miR-204. The UCA1-miR-204-CXCR4 regulatory network regulated the growth and metastasis of PCa, providing new insight in the management of patients with such malignancy.

Correlations of lncRNAs with cervical lymph node metastasis and prognosis of papillary thyroid carcinoma.

BackgroundCervical lymph node metastasis is an important prognostic indicator for papillary thyroid carcinoma (PTC) and affects treatment strategies for PTC. lncRNAs essentially contribute to the biological functions of tumors. This study aimed to identify the lncRNAs associated with cervical lymph node metastasis and prognosis of PTC and their potential pathophysiological mechanisms.Materials and methodsPTC-associated lncRNAs were selected from The Cancer Genome Atlas database, and correlations among lncRNAs, lymph node metastasis, tumor staging, and prognosis of PTC were analyzed in silico. These correlations were then validated through quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry (IHC).ResultsIn silico analysis showed that FAM95B1 and UCA1 were significantly correlated with cervical lymph node metastasis, tumor staging, and PTC prognosis (P<0.05). qRT-PCR analysis revealed high UCA1 expression in PTC tissues and correlations between UCA1 expression levels and cervical lymph node metastasis and tumor staging in PTC, that is, higher UCA1 expression resulted in poorer PTC prognosis. IHC analysis revealed that a high expression of UCA1 was accompanied by a high expression of metastasis-related proteins (MMP-2 and MMP-9), thereby validating the correlation of UCA1 expression with metastasis.ConclusionFAM95B1 and UCA1 expression was significantly correlated with the occurrence and progression of PTC. The expression levels of UCA1 significantly affected the prognosis of PTC patients and were significantly correlated with tumor staging and cervical lymph node metastasis.

Long non‑coding RNA UCA1 confers tamoxifen resistance in breast cancer endocrinotherapy through regulation of the EZH2/p21 axis and the PI3K/AKT signaling pathway.

Tamoxifen is the gold standard for breast cancer endocrinotherapy. However, drug resistance remains a major limiting factor of tamoxifen treatment. Long non‑coding (lnc) RNA serves an important role in drug resistance; however, the molecular mechanisms of tamoxifen resistance in breast cancer endocrinotherapy are largely unclear. lncRNA urothelial cancer associated1 (lncRNA UCA1, UCA1) has been proven to be dysregulated in human breast cancer and promotes cancer progression. In the present study, it was demonstrated that UCA1 was significantly upregulated in breast cancer tissues compared with healthy tissues. Furthermore, the expression level of UCA1 was significantly greater in tamoxifen‑resistant breast cancer cells (LCC2 and LCC9) when compared with those in the tamoxifen‑sensitive breast cancer cells (MCF‑7 and T47D). UCA1 silencing in LLC2 and LLC9 cells increased tamoxifen drug sensitivity by promoting cell apoptosis and arresting the cell cycle at the G2/M phase. Notably, the induced overexpression of UCA1 in MCF‑7 and T47D cells decreased the drug sensitivity of tamoxifen. The molecular mechanism involved in UCA1‑induced tamoxifen‑resistance was also investigated. It was identified that UCA1 was physically associated with the enhancer of zeste homolog2 (EZH2), which suppressed the expression of p21 through histone methylation (H3K27me3) on the p21 promoter. In addition, it was demonstrated that UCA1 expression was paralleled to the phosphorylation of CAMP responsive element binding protein (CREB) and AKT. When LCC2 cells were treated with the phosphoinositide 3‑kinase (PI3K)/protein kinaseB(AKT) signaling pathway inhibitor LY294002, the phosphorylation levels of CREB and AKT were significantly downregulated. Taken together, it was concluded that UCA1 regulates the EZH2/p21 axis and the PI3K/AKT signaling pathway in breast cancer, and may be a potential therapeutic target for solving tamoxifen resistance.

LncRNA UCA1 promotes cell proliferation, invasion and migration of laryngeal squamous cell carcinoma cells by activating Wnt/β-catenin signaling pathway.

In view of the poor prognosis of laryngeal squamous cell carcinoma (LSCC) and the functionality of long non-coding (lnc)RNA UCA1 in different types of cancer, the present study aimed to investigate the role of UCA1 in the development and progression of LSCC. A total of 90 patients with LSCC and 90 healthy subjects were enrolled in the present study. Expression levels of UCA1 in tumor tissues and adjacent healthy tissues, as well as serum of patients with LSCC and normal controls were detected by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of serum UCA1 for LSCC. Survival curves were plotted using the Kaplan-Meier method and employed to evaluate the prognosic values of serum UCA1 for LSCC. Cell proliferation, migration and invasion were detected using the cell proliferation assay, and Transwell migration and invasion assays, respectively. Expression levels of Wnt/β-catenin-associated proteins were detected by western blot analysis. Results indicated that the expression levels of UCA1 were significantly higher in tumor tissues compared with adjacent healthy tissues in the majority of patients with LSCC. In addition, serum levels of UCA1 were significantly higher in patients with LSCC coapred with healthy controls. UCA1 overexpression promoted, whereas UCA1 knockdown inhibited the proliferation, migration and invasion of LSCC cells. UCA1 overexpression activated the Wnt/β-catenin signaling pathway in LSCC cells, whereas treatment with Wnt inhibitor reduced the enhancing effects of UCA1 overexpression on the proliferation, migration and invasion of LSCC cells. The present findings suggest that UCA1 can promote cell proliferation, invasion and migration of LSCC cells by activating the Wnt/β-catenin signaling pathway.

Long noncoding RNA UCA1 promotes multiple myeloma cell growth by targeting TGF-β.

To investigate the role of long noncoding RNA (lncRNA) UCA1 in the multiple myeloma (MM) development. In samples of MM, the expression of UCA1 and TGF-β was investigated using real-time PCR. UCA1 lentiviral small hairpin RNA (shRNA) was transfected in MM cell lines. CCK-8 and colony formation assay were used to detect cell lines proliferation. The cell apoptosis assay was conducted to detect cell apoptosis. Western blot was utilized to detect the protein level of TGF-β. The expression level of UCA1 increased in MM samples and cell lines, and its high expression was associated with poor MM prognosis. Downregulation of UCA1 significantly inhibited cell lines proliferation and promoted cell apoptosis. UCA1 could positively regulate TGF-β in MM. Overexpression of TGF-β partially reversed the effect of UCA1 knockdown. UCA1 promotes MM cell lines proliferation by targeting TGF-β.

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.

LncRNA-UCA1 enhances MMP-13 expression by inhibiting miR-204-5p in human chondrocytes.

Osteoarthritis (OA) is a common degenerative disease characterized by degeneration of articular cartilage. Increasing studies showed that long noncoding RNAs (lncRNAs) play important roles in the cartilage damage. However, little is known about the role of UCA1 in the osteoarthritis. The expression level of UCA1 was upregulated in the OA cartilage. Overexpression of UCA1 suppressed the miR-204-5p expression in the chondrocytes. The expression of miR-204-5p was downregulated in the OA cartilage. Moreover, the expression of miR-204-5p was negatively correlated with the UCA1 expression in the OA cartilage. Elevated expression of UCA1 promoted the chondrocytes cell proliferation and overexpression of miR-204-5p suppressed chondrocytes cell proliferation. In addition, overexpression of UCA1 decreased the expression of the type II collagen and type IV collagen expression in the chondrocytes. Elevated expression of miR-204-5p promoted the type II collagen and type IV collagen expression in the chondrocytes. We idetified MMP-13 was a direct target gene of miR-204-5p in the chondrocytes. Overexpression of UCA1 enhanced the MMP-13 expression in the chondrocytes. Elevated expression of UCA1 regulated the chondrocytes cell proliferation and collagen expression through inhibiting the miR-204-5p expression.These results suggested that UCA1 played as an important regulator of survival and matrix synthesis of chondrocytes partly through suppressing the miR-204-5p expression.

Deregulated expression of long non-coding RNA UCA1 in multiple myeloma.

Long non-coding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that are not translated into proteins. They are involved in pathogenesis of many diseases including cancer and have a potential to serve as diagnostic and prognostic markers. We aimed to investigate lncRNA expression profiles in bone marrow plasma cells (BMPCs) of newly diagnosed multiple myeloma (MM) patients in comparison to normal BMPCs of healthy donors (HD) in a three-phase biomarker study. Expression profile of 83 lncRNA was performed by RT2 lncRNA PCR Array (Qiagen), followed by quantitative real-time PCR using specific TaqMan non-coding RNA assays analyzing 84 newly diagnosed MM patients and 25 HD. Our analysis revealed dysregulation of two lncRNAs; NEAT1 (sensitivity of 55.0% and specificity of 79.0%) and UCA1 (sensitivity of 85.0% and specificity of 94.7%). UCA1 levels correlated with albumin and monoclonal immunoglobulin serum levels, cytogenetic aberrations, and survival of MM patients. Our study suggests a possible prognostic impact of UCA1 expression levels on MM patients.

Deregulated Expression of Long Non-Coding RNAs UCA1, NEAT1 and BDNF-As in Multiple Myeloma

Introduction. Multiple myeloma (MM) is the second most common hematological malignancy in the world. It is characterized by increasing rate of various genetic mutations and dysregulated pathways. This work aims to find out if this phenomenon is also reflected in dysregulation of the so-called long non-coding RNA molecules (lncRNA). These molecules are over 200 nt long and primarily localized in the nucleus. It seems increasingly obvious that lncRNAs play a crucial role in human diseases and during hematopoiesis. Presumably, lncRNA affect hematological malignancies including MM by regulating the expression of oncogenes, tumor suppressor and key factors involved in hematopoiesis. We identified a disease-specific cellular lncRNA signature using a cohort of MM patients in comparison to healthy donors (HD).Methods. Fifty CD138+ samples obtained from newly diagnosed MM patients and HD were evaluated for this study. Total RNA was extracted from MM cells using miRNeasy Mini Kit or miRNeasy Micro Kit (all Qiagen) according to the manufacturer’s instructions. Concentration and purity of RNA were determined spectrophotometrically by NanoDrop ND-1000 (Thermo Scientific, USA). Screening analysis of 83 lncRNA was performed on 6 MM patients and 6 HD using RT2 lncRNA PCR Array - Human lncRNA Finder (Qiagen). Significantly deregulated lncRNAs between MM vs HD were validated by qPCR using relative quantification approach 2-ΔCt on a larger cohort of patients and HD. Briefly, High-capacity cDNA reverse transcription kit (Applied Biosystem, USA), was used to synthesize cDNA from 200 ng RNA according to the manufacturer’s recommendations. Expression levels of ZFAS1, UCA1, BDNF-AS, NEAT1 and FAS-AS1 were detected by RT-qPCR using TaqMan non-coding RNA assay (ZFAS1: Hs01379985_m1, FAS-AS1: Hs04233476_s1, BDNF-AS: Hs01010228_m1, UCA1: Hs01909129_s1, NEAT1: Hs03453535_s1), expression level of GAPDH using Human GAPD (GAPDH) Endogenous Control (VIC®/MGB probe, primer limited) and TaqMan Gene Expression Master Mix (all Applied Biosystem, USA). qPCR was performed using the Applied Biosystem 7500 Sequence Detection System. Analysis of the RT-qPCR data was performed using SDS version 2.0.1 software (Applied Biosystem, USA). Expression data from lncRNAs profiling were statistically evaluated in the environment of statistical language R by use of Bioconductor package and LIMMA approach combined with hierarchical clustering (HCL). P values were adjusted according to Bonferroni correction for multiple comparisons. Statistical differences between lncRNAs expression levels in MM patients and HD were evaluated by non-parametric Mann-Whitney U test. Receiver Operating Characteristic (ROC) analysis was used to calculate specificity and sensitivity of each lncRNA. P values <0.05 were considered significant.Results.RT2 lncRNA PCR Array profiling revealed 27 deregulated lncRNAs (all p<0.01) between MM patients and HD. ZFAS1, UCA1, BDNF-AS, NEAT1 and FAS-AS1 expression was further verified on a larger cohort of MM and HD samples. As the difference in ZFAS1 and FAS-AS1 expression between MM and HD was not significant (p=0.7; p=0.2, respectively), it was excluded from further analyses. UCA1 was significantly down-regulated (p<0.0001), NEAT1 and BDNF-AS were up-regulated in MM samples when compared with HD (both p<0.00000001). To discriminate MM from HD, receiver operating characteristic (ROC) curve was calculated. It revealed sensitivity of 100% (95%CI: 91.6 - 100.0) and specificity of 100% (95%CI: 63.1 - 100.0), and area under curve (AUC) = 1.000 for both, NEAT1 and BDNF-AS lncRNA expression and sensitivity of 95.24% (95%CI: 83.8 - 99.4) and specificity of 75.00% (95%CI: 34.9 - 96.8), and area under curve (AUC) = 0.905 for UCA1 expression levels (Fig. 1). We suppose that these dysregulated lncRNAs could have a biological relevance in MM since BDNF-AS is an antisense RNA for BDNF, a significant stimulating factor of osteoclasts in MM, NEAT1 and UCA1 were described as dysregulated in several types of cancer, including hematological malignancies. Further validations are currently ongoing.Conclusions. Altogether, our first observations demonstrate that cellular lncRNA UCA1, NEAT1 and BDNF-AS may be involved in pathophysiological processes occurring in MM cells and prompt further studies in this field.Grant support: AZV 15-29508A [Display omitted] DisclosuresHajek:Onyx: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Novartis: Research Funding.

Prognostic value of long non-coding RNA UCA1 in human solid tumors.

BackgroundNumerous studies have shown that the expression of UCA1 was aberrantly upregulated in various cancer types. High expression of UCA1 was reported to be associated with unfavorable prognosis in cancer patients.ResultsA total of 1240 patients from 15 articles were included. The results indicated that a significantly shorter OS was observed in patients with high expression level of UCA1 (HR = 1.71, 95% CI: 1.43–1.99), in the subgroup analysis, the association was also observed in patients with cancers of digestive system (HR = 2.12, 95% CI: 1.59–2.66). Statistical significance was also observed in subgroup meta-analysis stratified by the cancer type, cut-off value, analysis type and sample size. Furthermore, poorer DFS was observed in patients with high expression level of UCA1 (HR = 2.54; 95% CI: 1.09–4.00). Additionally, the pooled odds ratios (ORs) showed that increased UCA1 was also related to positive lymph node metastasis (OR = 2.98, 95% CI: 2.06–4.30), distant metastasis (OR = 3.14, 95% CI: 1.77–5.58) and poor clinical stage (OR = 2.76, 95% CI: 2.08–3.68).Materials and MethodsA comprehensive retrieval was conducted in multiple databases, including PubMed, Embase, Web of Science and CNKI. We collected relevant articles to explore the association between the expression levels of UCA1 and prognosis.ConclusionsHigh expression level of UCA1 was associated with poor clinical outcome. UCA1 could serve as a novel biomarker for prognosis and might be a potential predictive factor for clinicopathological characteristics in various cancers. Further studies should be performed to verify the clinical utility of UCA1 in human solid tumors.