LOC285194 Expression Research Articles

Long Non-coding RNA LOC285194 Promotes Epithelial Ovarian Cancer Progression via the Apoptosis Signaling Pathway.

To explore the molecular mechanism and clinical significance of a newly identified lncRNA LOC285194 in epithelial ovarian cancer (EOC). LOC285194 transcript levels were analyzed in EOC cells compared to normal cells. Small interfering RNAs were used to suppress LOC285194 expression. Levels of apoptosis-related proteins were determined by western blot. LOC285194 expression in ovarian cancer and non-tumor tissues were compared with clinicopathologic and survival data. Knockdown of LOC285194 decreased cell migration and proliferation, enhanced reactive oxygen species production and resulted in increased levels of proteins of the extrinsic apoptotic signaling pathway. LOC285194 expression level was higher in ovarian cancer tissues compared to control. Overall survival was significantly shorter in patients with high LOC285194 expression. Lymph node metastasis and high LOC285194 expression were significant prognostic factors of mortality (HR=4.614 and 5.880; p=0.026 and p=0.002, respectively). LOC285194 can promote the progression of EOC via an anti-apoptotic mechanism. It may serve as a novel biomarker for predicting prognosis of EOC.

LOC285194 inhibits proliferation of human keratinocytes through regulating miR-616/GATA3 pathway

LncRNA LOC285194 has been associated with the occurrence of psoriasis. However, the underlying mechanisms that lead to psoriasis remain unclear. In this study, the expression of LOC285194, miR-616, and GATA3 was determined by western blotting and quantitative real-time PCR, and their relationships were assessed using dual-luciferase reporter assays. The effects of LOC285194 on the proliferation and apoptosis of keratinocytes were investigated using cell counting kit-8 assays and flow cytometry, respectively. Reduced expression of LOC285194 was detected in the skin lesion samples from patients with psoriasis. Overexpression of LOC285194 led to reduced cell viability, cell cycle arrest, and increased cell apoptosis in keratinocytes, whereas LOC285194 silencing resulted in opposite effects. In addition, LOC285194 was found to negatively regulate miR-616, which modulated GATA3 expression through its direct binding to the 3′-untranslated region of GATA3. Knockdown of GATA3 rescued LOC285194 overexpression-mediated cell viability reduction, cell cycle arrest and apoptosis induction in keratinocytes. Taken together, LOC285194 was found to inhibit keratinocyte growth by sponging miR-616 that regulates GATA3.

Long non-coding RNA LOC285194 inhibits proliferation and migration but promoted apoptosis in vascular smooth muscle cells via targeting miR-211/PUMA and TGF-β1/S100A4 signal

ABSTRACT Long non-coding RNA LOC285194 (LOC285194) has reported to regulate vascular smooth muscle cells (VSMCs) proliferation and apoptosis in vitro and in vivo. Here we aimed to determine the role of LOC285194 in the proliferation, migration and apoptosis of VSMCs and its underlying mechanisms. A7r5 cells were transfected with Lv-LOC285194 or control Lv-NC for 24–72 h, or small interfering RNA targeting S100A4 (S100A4 siRNA) for 24–48 h, or co-transfected with Lv-LOC285194 and PUMA siRNA for 72 h, or treated with miR-211 inhibitor or co-transfected with Lv-LOC285194 and miR-211 mimics for 72 h. A7r5 cells were also treated with transforming growth factor – β(TGF-β) (5 ng/ml) after Lv-LOC285194 transfection for 24 h. The relationship between LOC285194 and TGF-β was confirmed using luciferase reporter assay. Cell proliferation and cell apoptosis were analyzed by Cell Counting Kit-8 (CCK-8) assay, ELISA and TUNEL staining. LOC285194 and miR-211 expression were detected by qPCR assay. S100A4, pro-apoptotic and anti-apoptotic protein were detected by Western blot assay. LOC285194 inhibited cell proliferation, invasion and migration and promoted cell apoptosis accompanied by upregulation of PUMA and downregulation of miR-211 and S100A4. Targeting PUMA reversed the effect of LOC285194 on cell apoptosis and proliferation. miR-211 mimic inhibited LOC285194-induced PUMA upregulation and decreased LOC285194-induced cell apoptosis. TGF-β (5 ng/ml) treatment reversed S100A4 siRNA or LOC285194-induced S100A4 expression. Luciferase reporter assay showed that TGF-β was the target of LOC285194. LOC285194 inhibits proliferation and promoted apoptosis in vascular smooth muscle cells via targeting miR-211/PUMA signal; In addition, LOC285194 decreased cell invasion and migration by targeting TGF-β1/S100A4 signal.

Long non-coding RNA LOC285194 regulates vascular smooth muscle cell apoptosis in atherosclerosis

ABSTRACT Long non-coding RNAs (lncRNAs) recently have been implicated in many biological processes and diseases. Atherosclerosis is a major risk factor for cardiovascular disease. However, the functional role of lncRNAs in atherosclerosis is largely unknown. Here we identified LOC285194 as a key regulator of cell proliferation and apoptosis during atherosclerosis. The expression of LOC285194 was dramatically down-regulated in a aortic atherosclerotic plaques of well-defined model of apolipoprotein-E knockout (ApoE−/-) mice. Moreover, we found that targeting LOC285194 results in neointimal hyperplasia in vivo in carotid artery injury model. We also showed that targeting LOC285194 promotes cell proliferation and inhibits apoptosis in vascular smooth muscle cells (VSMCs) in vitro, and vice versa. In addition, targeting LOC285194 promotes cell invasion and migration in vitro. Our studies identify LOC285194 as a novel regulator of cell proliferation and apoptosis and suggest that this lncRNA could serve as a therapeutic target to treat atherosclerosis and related cardiovascular disorders.

Long Noncoding RNA loc285194 Expression in Human Papillomavirus-Positive and -Negative Cervical Squamous Cell Carcinoma, C33A, and SiHa Cells and Transforming Growth Factor-β1.

BackgroundThis study aimed to investigate the expression of long noncoding RNA (lncRNA) loc285194 in cervical squamous cell carcinoma (CSCC) biopsies that were positive and negative for human papillomavirus (HPV) and in human CSCC cell lines SiHa and C33A and to investigate the overexpression of lncRNA loc285194.Material/MethodsCervical biopsy tissue and plasma samples from 66 patients with histologically confirmed CSCC, that were HPV16-positive (N=22), HPV18-positive (N=27), and HPV-negative (N=17), and healthy controls (N=20) and human CSCC cell lines SiHa (HPV16-positive) and C33A (HPV-negative) were studied. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure the expression of lncRNA loc285194 in cervical biopsies and plasma. Enzyme-linked immunosorbent assay (ELISA) and Western blot were used to measure levels of transforming growth factor-β1 (TGF-β1). A lncRNA loc285194 expression vector was constructed and transfected into SiHa and C33A cells that underwent a transwell assay for cell migration.ResultsExpression of lncRNA loc285194 was downregulated in HPV-positive and HPV-negative tissue samples and plasma from patients with CSCC and distinguished between patients and healthy controls. Plasma levels of loc285194 and TGF-β1 were significantly correlated with the presence of CSCC. In SiHa and C33A cells, TGF-β1 expression was downregulated, and cell migration was inhibited following lncRNA loc285194 overexpression. Although lncRNA loc285194 expression was not affected by TGF-β1 treatment, its effects on cell migration were reduced by TGF-β1.ConclusionsThe expression of lncRNA loc285194 inhibited the migration of CSCC cells in vitro through the inactivation of TGF-β1.

Decreased expression of long non-coding LOC285194 predicts tumour progression and poor prognosis of hepatocellular carcinoma after curative hepatectomy

BackgroundLong non-coding RNAs (LncRNAs) have been recently implicated as having oncogenic and tumour suppressor roles. LncRNA LOC285194 (LOC285194) expression was significantly reduced in a variety of tumour tissues and cell...

LncRNA loc285194 inhibits tumor growth of laryngeal squamous cell carcinoma cells by downregulating hexokinase 2.

LncRNA loc285194 is a well-characterized tumor suppressor in several types of cancer. To the best of our knowledge, the present study is the first to investigate the involvement of lncRNA loc285194 in laryngeal squamous cell carcinoma (LSCC). The expression of loc285194 and hexokinase 2 (HK-2) mRNA in laryngeal biopsies of patients with LSCC or healthy controls was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The diagnostic value of loc285194 and HK-2 mRNA for LSCC was evaluated using receiver operating characteristic curve analysis. The correlation between expression of loc285194 and HK-2 mRNA was analyzed using the Pearson correlation coefficient. The association between loc285194 and clinicopathological data of patients with LSCC was analyzed using the Chi-square test. LncRNA loc285194 and HK-2 expression vectors were transfected into human LSCC cell lines and the effects on HK-2 expression, lncRNA loc285194 expression and cell proliferation was detected by western blot, RT-qPCR and CCK-8 assays, respectively. It was observed that loc285194 was upregulated, while HK-2 mRNA was downregulated in patients with LSCC compared with healthy controls. The results demonstrated that the downregulation of loc285194 may be a sensitive diagnostic marker for LSCC. The expression levels of loc285194 and HK-2 mRNA were inversely correlated in patients with LSCC, but not in healthy controls. loc285194 expression was significantly associated with tumor size, but not distant tumor metastasis. Loc285194 overexpression significantly inhibited HK-2 expression and LSCC cell proliferation. HK-2 overexpression did not significantly affect Loc285194 expression, but promoted LSCC proliferation and attenuated the inhibitory effects of loc285194 overexpression on LSCC cell proliferation. lncRNA loc285194 may inhibit tumor growth of LSCC cells by downregulating HK-2.

Decreased expression of lncRNA loc285194 as an independent prognostic marker in cancer: A systematic review and meta-analysis

BackgroundSeveral studies have indicated that lncRNA loc285194 is aberrantly expressed in many types of cancer. This meta-analysis was performed to elucidate the potential role of lncRNA loc285194 as a prognostic marker in malignant tumors. MethodsAn electronic search of PubMed, Medline, Embase, and Web of Science was performed to identify all eligible papers related to the prognostic impact of lncRNA loc285194 expression in cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted from the included studies to explore the association between lncRNA loc285194 expression and patient overall and disease-free survival (OS & DFS). The odds ratios (ORs) were also calculated to assess the association between lncRNA loc285194 expression and clinicopathological parameters. ResultsA total of 14 eligible articles with 1215 patients were included in this meta-analysis. Meta-results revealed that low expression of lncRNA loc285194 was significantly correlated with poorer overall survival (OS; HR = 2.34; 95% CI, 1.78–3.06; P < 0.001) and disease-free survival (DFS; HR = 2.66; 95% CI, 1.95–3.64; P = 0.001) rates in cancer patients. Low lncRNA loc285194 expression was also found to be significantly associated with lymph node metastasis (LNM; OR = 2.17; 95% CI, 1.23–3.83; P = 0.007), and distant metastasis (DM; OR = 2.49; 95% CI, 1.26–4.91; P = 0.009). ConclusionsThis study demonstrated that decreased level of lncRNA loc285194 was associated with poor clinical outcomes for patients with different types of cancer, supporting a promising potential biomarker for prognosis and metastasis in human cancers.

Long non-coding RNA LOC285194 functions as a tumor suppressor by targeting p53 in non-small cell lung cancer.

Recently, LOC285194 has shown a potential tumor-suppressor function in several types of human cancers, but its function in non-small cell lung cancer (NSCLC) remains unknown. This study intended to investigate the biological role of LOC285194 and its clinical significance in NSCLC. LOC285194 was detected by qRT-PCR, and its correlation with clinicopathological features of NSCLC was analyzed. The expression of LOC285194 was knocked down or ectopically expressed in lung cancer cells (A549 and H1299) and tumor cell growth, migration and invasion in vitro were investigated. In addition, the interaction of LOC285194 and target proteins was assessed by RNA pulldown and RNA immunoprecipitation in vitro. The results revealed that the expression of LOC285194 was significantly lower in tumor tissues when compared with the corresponding non-tumor tissues (P<0.001). Its expression was correlated with the tumor size (P=0.027). Kaplan-Meier analysis revealed that patients with lower LOC285194 expression had worse disease-free survival and overall survival rates (P<0.05). RNA protein interaction analysis revealed that p53 was the direct binding target of LOC285194 in NSCLC. Bioinformatics analyses suggested that depletion of LOC285149 could affect its antitumor function through the KRAS/BRAF/SMEK pathway. Our findings indicated that LOC285194 was a novel non-coding prognostic indicator and contributed to tumor suppression by targeting p53 in NSCLC, suggesting that it may be a non-coding target for NSCLC gene therapy.

Abstract 3544: Tumor suppressor function of loc285194 in breast cancer

Abstract Accumulating studies have focused on the oncogenic and tumor suppressive roles of the newly identified lncRNAs. LOC285194 was found to be associated with poor survival of osteosarcoma patients and colorectal cancer patients. Also loc285194 is reported to be a direct transcription target of p53 and could suppress cell growth. However, its role in breast cancer (BC) remains unknown. The aim of this study was to examine the expression pattern of loc285194 in BC and to evaluate its biological role and clinical significance in prediction of prognosis. In this study, we examined expression of loc285194 in 20 pairs of BC cancer tissues and adjacent noncancerous tissues (ANCT), also in 151 BC tissues, 14 BC cell lines and one normal breast cell line. It showed that loc285194 expression was lower both in BC samples and in BC cell lines compared with corresponding normal control. Loc285194 expression was correlated with menopausal status. Postmenopausal patients had a lower loc285194 expression level comparing with premenopausal patients (p=0.040). Moreover, low loc285194 expression was correlated with a relatively poor survival status (p=0.023) and a poor tumor differentiation (p=0.035). The Kaplan-Meier survival curves indicated that the overall survival (OS) was significantly poor in BC patients who showed low loc285194 expression. Furthermore, expression of loc285194 is significantly associated with worse prognosis independent of prognostic markers in estrogen receptor (ER) negative tumor samples (p = 0.05). Our studies indicate that loc285194 may represent a new marker of prognosis and it is a potential therapeutic target for breast cancer especially for ER negative breast cancer. Citation Format: YAYUN CHI, Sheng Huang, Jiong Wu. Tumor suppressor function of loc285194 in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3544. doi:10.1158/1538-7445.AM2014-3544

Association of decreased expression of long non-coding RNA LOC285194 with chemoradiotherapy resistance and poor prognosis in esophageal squamous cell carcinoma.

BackgroundExpression of the long non-coding RNA (lncRNA) LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of the present study was to explore the relationship between LOC285194 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC), so as to assess whether it could be a novel biomarker for prognosis and prediction of response to therapy on ESCC patients.MethodsThe method of quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure LOC285194 expression in pretreatment biopsy specimens and matched normal tissue derived from ESCC patients who underwent preoperative chemoradiotherapy followed by surgical resection (CRT + S group; n = 55) or from those who received surgical resection alone (S group; n = 87). The association between LOC285194 expression and clinicopathological features and prognosis were then analyzed.ResultsLOC285194 expression was significantly down-regulated in ESCC tumor tissues when compared with the adjacent normal tissues (p < 0.001). Low expression of LOC285194 was associated with larger tumor size (p = 0.002), advanced TNM stage (p = 0.018), more lymph node metastases (p = 0.013) and distant metastases (p = 0.015). In the CRT + S group, the pathological complete response rate was 57% (16/28) for the LOC285194-high group, and 15% (4/27) for the LOC285194-low group. Univariate analysis revealed that low expression of LOC285194 was significantly correlated with CRT response (p = 0.002). Moreover, Kaplan-Meier survival analysis revealed that patients with low expression of LOC285194 had a decreased disease free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Multivariable analysis further identified low expression of LOC285194 as an independent prognosis factor for CRT response (p = 0.011), DFS (p < 0.001) and OS (p = 0.002).ConclusionDecreased expression of LOC285194 could serve as a molecular marker to predict the clinical outcome of ESCC patients after surgery, and select patients who would benefit from preoperative CRT.

Low expression of LOC285194 is associated with poor prognosis in colorectal cancer

BackgroundThe long non-coding RNAs (lncRNAs) study has gradually become one of the hot topics in the field of RNA biology. One lncRNA which has attracted attention is LOC285194, a lncRNA demonstrated the potential tumor-suppressor role in osteosarcoma. The aim of this study was to examine the expression of LOC285194 in colorectal cancer (CRC) patients and to investigate the relationship between this lncRNA levels and existing clinicopathologic parameters and patient survival.MethodsThe expression of LOC285194 was detected by quantitative real-time polymerase chain reaction in pairs of tumorous and adjacent normal tissues of 81 colorectal cancer patients with a follow-up of 5 years, as well as in three colorectal cancer cell lines and normal intestinal mucous cell line. Then, we analyzed the potential relationship between this lncRNA levels in tumor tissues and existing clinicopathological features of CRC, and clinical outcome.ResultsThe relative expression levels of LOC285194 was significantly lower in tumor tissues (p < 0.001) and colorectal cancer cell lines compared with adjacent normal tissues and normal intestinal mucous cell line. In addition, low expression of LOC285194 was correlated with larger tumor size (p = 0.015), higher tumor stage (p = 0.034), and more distant metastasis (p = 0.046). Kaplan-Meier analysis indicated that patients with low LOC285194 expression had a poor disease free survival (p = 0.010). Moreover, multivariate analysis showed that decreased expression of LOC285194 was an independent predictor of disease-specific survival.ConclusionOur data indicate that LOC285194 might be a novel prognostic indicator in colorectal cancer and may be a potential target for diagnosis and gene therapy.

LncRNA loc285194 is a p53-regulated tumor suppressor

Protein-coding genes account for only a small part of the human genome, whereas the vast majority of transcripts make up the non-coding RNAs including long non-coding RNAs (lncRNAs). Accumulating evidence indicates that lncRNAs could play a critical role in regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. LncRNA loc285194 was previously shown to be within a tumor suppressor unit in osteosarcoma and to suppress tumor cell growth. However, it is unknown regarding the regulation of loc285194. Moreover, the underlying mechanism by which loc285194 functions as a potential tumor suppressor is elusive. In this study, we show that loc285194 is a p53 transcription target; ectopic expression of loc285194 inhibits tumor cell growth both in vitro and in vivo. Through deletion analysis, we identify an active region responsible for tumor cell growth inhibition within exon 4, which harbors two miR-211 binding sites. Importantly, this loc285194-mediated growth inhibition is in part due to specific suppression of miR-211. We further demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to loc285194, miR-211 promotes cell growth. Finally, we detect downregulation of loc285194 in colon cancer specimens by quantitative PCR arrays and in situ hybridization of tissue microarrays. Together, these results suggest that loc285194 is a p53-regulated tumor suppressor, which acts in part through repression of miR-211.

Abstract 3400: Recurrent focal copy-number changes and loss-of-heterozygosity implicate two non-coding RNAs and one tumor-suppressor gene at chromosome 3q13.31 in osteosarcoma

Abstract Osteosarcomas are copy-number alteration (CNA)-rich malignant bone tumors. Using microarrays, fluorescence in-situ hybridization and quantitative polymerase chain reaction we characterize a focal region of chr3q13.31 (osteo3q13.31) harboring CNAs in 80% of osteosarcomas. As such, osteo3q13.31 is the most altered region in osteosarcoma and contests the view that CNAs in osteosarcoma are non-recurrent. Most (67%) osteo3q13.31 CNAs are deletions, 75% of which are mono-allelic, and are frequently accompanied by loss-of-heterozygosity (LOH) in flanking DNA. These CNAs often involve the non-coding RNAs (ncRNAs) LOC285194 and BC040587, and sometimes, the limbic system-associated membrane protein (LSAMP) tumor suppressor (TS). Change in expression of osteo3q13.31 genes is ubiquitous in osteosarcoma, usually involving loss of expression. Underscoring the functional significance of osteo3q13.31 CNAs, expression of LOC285194 and BC040587 and sometimes LSAMP, correlates with the presence of osteo3q13.31 CNAs. Focal osteo3q13.31 CNAs and LOH are also common in cell lines from other cancers, identifying osteo3q13.31 as a universal candidate TS region. Osteo3q13.31 genes may function as a unit, since we demonstrate significant correlation between the expression of distantly spaced LSAMP, LOC285194, and BC040587. Supporting this notion, depletion of either LSAMP or LOC285194 promotes proliferation of normal osteoblasts through regulation of apoptotic and cell cycle transcripts, and vascular endothelial growth factor (VEGF)/VEGF receptor 1 (VEGFR1). Furthermore, the presence of LOC285194 or BC040587 deletions in tumor DNA is associated with poor survival of osteosarcoma patients. Osteo3q13.31 therefore represents a novel universal TS region containing several cooperatively acting genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3400.