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

BACKGROUND/AIM: To explore the molecular mechanism and clinical significance of a newly identified lncRNA LOC285194 in epithelial ovarian cancer (EOC). MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: LOC285194 can promote the progression of EOC via an anti-apoptotic mechanism. It may serve as a novel biomarker for predicting prognosis of EOC.

Long Non-coding RNA Signature for Liver Metastasis of Colorectal Cancers.

Colorectal cancer ranks within the top three cancers both in terms of incidence as well as deaths. Metastasis is often the major cause of mortality and liver is the primary and most common site to which colorectal cancers metastasize. We tested the prognostic ability of a long non-coding RNA (lncRNA) signature in liver metastatic colorectal cancers. We first evaluated expression levels of several lncRNAs in eight excised liver metastases from primary colorectal cancers and found significantly upregulated lncRNAs HOTAIR and MALAT1 along with significantly downregulated LOC285194. We further compared the expression levels of HOTAIR, MALAT1 and LOC285194 in primary colorectal tumors at the time of initial diagnosis and correlated them with disease progression and liver metastasis. HOTAIR and MALAT1 were significantly upregulated and LOC285194 was significantly downregulated in twelve patients who were diagnosed with liver metastasis within 5 years of initial diagnosis, compared to the five patients with no metastasis. A positive signature comprising of high HOTAIR/MALAT1 and low LOC285194 also correlated with progression to higher grade tumors. Thus, the lncRNA signature comprising of high HOTAIR/MALAT1 and low LOC285194 could be a prognostic signature for liver metastasis as well as overall poor survival.

Long non-coding RNA LOC285194 inhibits proliferation and migration but promoted apoptosis in vascular smooth muscle cells via targeting miR-211/PUMA and TGF-ß1/S100A4 signal.

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 - ß(TGF-ß) (5 ng/ml) after Lv-LOC285194 transfection for 24 h. The relationship between LOC285194 and TGF-ß 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-ß (5 ng/ml) treatment reversed S100A4 siRNA or LOC285194-induced S100A4 expression. Luciferase reporter assay showed that TGF-ß 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-ß1/S100A4 signal.

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.

Propofol inhibits migration and induces apoptosis of pancreatic cancer PANC-1 cells through miR-34a-mediated E-cadherin and LOC285194 signals.

Propofol has exhibited potent antitumor activity in pancreatic cancer cells in vitro and in vivo. The study aimed to investigate the anti-tumor mechanisms of propofol on pancreatic cancer PANC-1 cells in vitro. PANC-1 cells were exposure to concentration 20 µg/ml of propofol for 72 h. Long non-coding RNA LOC285194 siRNA LOC285194 siRNA, E-cadherin siRNA and microRNA-34a (miR-34a) inhibitor were used to investigate the effect of propofol on PANC-1 cells. miR-34a and LOC285194 were analyzed by quantitative real-time PCR (qRT-PCR). Pro-apoptotic protein bax, cleaved-caspase-3 and anti-apoptotic protein bcl-2 were analyzed by Western blot. Cell viability and cell apoptosis were detected by MTT and TUNEL staining, respectively. Cell migration was detected by wound-healing assay. The results showed that propofol upregulated miR-34a expression, which, in turn, upregulated LOC285194 expression, resulting in PANC-1 cell apoptosis and growth inhibition. In addition, propofol upregulated miR-34a expression, which, in turn, upregulated E-cadherin expression, resulting in cell migration inhibition. Our research confirmed that propofol-induced cell apoptosis and inhibited cell migration in PANC-1 cells in vitro via promoting miR-34a-dependent LOC285194 and E-cadherin upregulation, respectively.

LncRNA LOC285194 modulates gastric carcinoma progression through activating Wnt/ß-catenin signaling pathway.

Emerging evidences have revealed long noncoding RNAs (lncRNAs') critical roles in diverse human carcinoma. Among these cancers, lncRNA LOC285194 has been extensively investigated in several types of carcinomas in the recent years. Nevertheless, the biological function, clinical relevance, and the influence of LOC285194 in gastric cancer (GC) are not fully understood. The present study aims to explore the biological function of LOC285194 in the progression and development of GC. First, LOC285194 expressions were detected in GC tissues and cell lines. The functional role of LOC285194 in GC was evaluated both in vitro and in vivo. Our data found that LOC285194 was lowly expressed both in human GC tissues and GC cell lines compared with corresponding normal controls. Moreover, LOC285194 was mitigated by transfection with LV-LOC285194 in both HGC-27 and MKN45 cell lines. Silencing of LOC285194 remarkably induced GC cell livability and cell proliferation. On the contrary, the LOC285194 overexpression suppressed MKN45 and HGC-27 cell proliferation and promoted cell apoptosis. Additionally, silencing of LOC285194 increased the ability of colony formation, cell migration, and invasive capacities, together with blocking the apoptotic rates of GC cells. Correspondently, LOC285194 overexpression exerted the opposite effects. Mechanistically, silencing of LOC285194 promoted GC progression via inducing Wnt signaling activity. Moreover, in vivo xenografts nude mice model results showed that LOC285194 inhibited GC progression through targeting Wnt signaling. Taken together, LOC285194 is associated with GC progression by regulating the Wnt signaling transduction, potentiating LOC285194's promising role as a novel treatment biomarker in GC.

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

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 non-coding RNA LOC285194 in cancer.

Long non-coding RNAs (lncRNAs) are non-protein-encoding RNAs that are usually over 200 nucleotides-long. The development of whole-genome sequencing has enabled the identification of several lncRNAs, and the determination of their critical roles in the human tumor process. LOC285194, also known as LSAMP antisense RNA 3 and tumor suppressor candidate 7 (TUSC7), is a >2-kb-long lncRNA comprised of four exons (gene ID: 285194), and located in chr3q13.31. LOC285194 expression is reported to be consistently low in tumor cells and often associated with poor clinical outcomes. Functionally, LOC285194 overexpression has been shown to inhibit cell proliferation, invasion, and migration in vitro and in vivo. Further, LOC285194 mainly suppressed or promoted the expression of related genes through direct or indirect pathways, suggesting that LOC285194 might be a feasible biomarker or therapeutic target in human cancers. Here, we reviewed and summarized existing literature on the functions and mechanisms of LOC285194 in human cancers.

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

BACKGROUND: Long 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 lines, which promotes cell proliferation and migration. The aim of the present study is to examine the expression pattern of LOC285194 and its clinical significance in hepatocellular carcinoma (HCC) patients after curative liver resection. MATERIALS AND METHODS: We examined the expression of LOC285194 in 120 HCC samples and controls from adjacent non-tumour tissues using real-time quantitative reverse transcription-PCR and analysed its correlation with clinical parameters and prognosis in these patients who have undergone curative hepatic resection with a median follow-up of 3.5 years. RESULTS: The expression level of LOC285194 was significantly lower in tumour tissues and four liver cancer cell lines compared with adjacent normal tissues and normal liver cell line. Furthermore, a low expression of LOC285194 was significantly correlated with advanced tumour stage, microvascular invasion, tumour number and differentiation. Additionally, survival analysis showed that patients with low LOC285194 expression had a significantly worse overall and disease-free survival. Moreover, univariate and multivariate analyses showed that decreased expression of LOC285194 was an independent predictor of long-term survival. CONCLUSIONS: The low expression level of LOC285194 might be a novel candidate biomarker for predicting tumour progression and poor prognosis in HCC patients who have undergone hepatectomy and might be a potential target for gene therapy.

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.

BACKGROUND: Several 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. METHODS: An 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. RESULTS: A 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). CONCLUSIONS: This 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.

Expression and clinical significance of long chain non-coding RNA LOC285194 in human breast cancer tissue / 重庆医学

Objective To investigate the expression of long chain non-coding(lnc) RNA LOC285194 in breast cancer tissue and paracancerous tissue and its clinical significance.Methods Forty-two samples of paraffin embedded breast cancer tissue and 16 samples of paraffin embedded paracancerous tissue were selected.The expression of lncRNA LOC285194 in these tissue were detected by using quantitative real-time polymerase chain reaction(PCR).Then its correlation with clinicopathological features was analyzed.Results The expression level of lncRNA LOC285194 in breast cancer tissue was significantly lower that in the paracancerous tissue (P＜0.01);the level of lncRNA LOC285194 in human epidermal growth factor receptor-2(HER2)overexpression tissues was up-regulated compared with HER2 negative breast cancer tissue(P =0.013),there was a positive correlation between them(r=0.385,P=0.012).Conclusion lncRNA LOC285194 may play the role of cancer suppressor gene and may be involved in the generation of breast cancer by HER2 association,which may become a target gene of breast cancer treatment.

Expression of long non-coding RNA LOC285194 and its prognostic significance in human pancreatic ductal adenocarcinoma.

INTRODUCTION: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. lncRNA LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of this study was to investigate relationship between LOC285194 expression and clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). METHODS: Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of lncRNA LOC285194 in human PDAC cells and tissue samples. The association of LOC285194 expression with clinicopathologic features was analyzed. Kaplan-Meier analyses were used to assess survival of patients. Univariate and multivariate analyses were performed using the Cox proportional hazards model to analyze the prognostic significance of LOC285194 expression. RESULTS: Our data showed that the relative level of LOC285194 in PDAC cells was significantly lower than that in normal human pancreatic duct epithelial cell line. Also, the expression of LOC285194 in PDAC tissues was significantly lower than that in adjacent non-tumor tissues. By statistical analyses, low LOC285194 expression was observed to be closely correlated with clinical stage, lymphnode metastasis and liver metastasis. Kaplan-Meier survival analysis revealed that patients with low LOC285194 expression had a poor overall survival compared with the high LOC285194 group (P < 0.05). Univariate and multivariate analyses showed that low LOC285194 expression was an independent poor prognostic factor for PDAC patients. CONCLUSIONS: Our data provided the first evidence that reduced LOC285194 in PDAC tissues was correlated with tumor progression, and lncRNA LOC285194 might be a potential molecular biomarker for predicting the prognosis of patients.