Plasma lncRNA Research Articles

LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression.

The aim of this study was to detect the expression of long non-coding ribonucleic acid (lncRNA) urothelial carcinoma associated 1 (UCA1) in the plasma of patients with osteoporosis (OST), and to investigate its influences on the proliferation and differentiation of osteoblasts and its mechanism. Plasma samples were collected from 52 OST patients treated in our hospital and 30 healthy subjects receiving a physical examination, respectively. The expression level of lncRNA UCA1 in OST patients and healthy subjects were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Furthermore, osteoblast MC3T3-E1 cell lines with a stable knockout of UCA1 in mice were constructed using small-interfering RNA (siRNA). The influence of UCA1 knockout on the proliferation of osteoblasts was detected using cell counting kit-8 (CCK-8) assay. Meanwhile, the proportion of EdU-positive cells in osteoblasts of the control group and UCA1 knockout group was detected using EdU staining. Moreover, the messenger RNA (mRNA) levels of differentiation-related genes, including Runt-related transcription factor 2 (Runx2), Collagen1α1, osteoclast (OC), osteoprotegerin (OPG), osteopontin (OPN) and Osterix (OSX), were detected via RT-PCR. The protein expression level of Runx2 was detected via Western blotting. In addition, osteoblasts were cultured with a bone-derived medium for 14 d. Then, the differentiation status was detected via alizarin red staining and alkaline phosphatase staining. Finally, the expression of bone morphogenetic protein-2 (BMP-2)/(Smad1/5/8) signaling pathway was analyzed using Western blotting. The expression of plasma lncRNA UCA1 was significantly increased in OST patients (p<0.05). Cell experiments revealed that UCA1 siRNA intervention could significantly promote the proliferation and differentiation of osteoblast MC3T3-E1 cell lines. In addition, Western blotting showed that the pro-apoptotic effect of UCA1 might be mediated by the BMP-2/(Smad1/5/8) signaling pathway in osteoblasts. Inhibiting lncRNA UCA1 can promote the proliferation and differentiation of osteoblasts by activating the BMP-2/(Smad1/5/8) signaling pathway in osteoblasts. Therefore, UCA1 is expected to be a new therapeutic target for OST.

Long non‑coding RNA SLNCR1 regulates non‑small cell lung cancer migration, invasion and stemness through interactions with secretory phospholipase A2.

Long non-coding RNA (lncRNA) SRA-like non-coding RNA (SLNCR1; also known as linc00673) is a recently identified oncogenic lncRNA. The role of SLNCR1 in non-small cell lung cancer (NSCLC), a common malignancy, remains poorly understood. The present study aimed to investigate the involvement of long non-coding RNA SLNCR1 in the pathogenesis of NSCLC. Reverse transcription-quantitative PCR (RT-qPCR) and ELISA were performed to measure the levels of lncRNA SLNCR1 and secretory phospholipase A2 (sPLA2) in lung biopsies, respectively. Correlations between expression levels of lncRNA SLNCR1 and sPLA2 were analyzed by Pearson's correlation analysis. Diagnostic value of lncRNA SLNCR1 for NSCLC was evaluated by receiver operating characteristic curve analysis. lncRNA SLNCR1 small interfering (si)RNA and sPLA2 overexpression vector were transfected into NSCLC cells. Cell migration, invasion and stemness were examined by Transwell migration assay, Matrigel invasion assay and flow cytometric assay, respectively. Following transfection, expression of lncRNA SLNCR1 and sPLA2 was detected by RT-qPCR and western blotting, respectively. The results demonstrated that lncRNA SLNCR1 expression levels were upregulated in tumor tissues compared with adjacent healthy tissues of patients with NSCLC. Plasma lncRNA SLNCR1 and sPLA2 expression levels were upregulated in patients with NSCLC compared with healthy controls. Plasma lncRNA SLNCR1 and sPLA2 were positively correlated in patients with NSCLC, but not in healthy controls. lncRNA SLNCR1 siRNA silencing inhibited, whereas sPLA2 overexpression promoted cell migratory and invasive abilities and stemness. lncRNA SLNCR1 siRNA silencing led to downregulated sPLA2 expression, whereas sPLA2 overexpression did not significantly affect lncRNA SLNCR1 expression. sPLA2 overexpression attenuated the inhibitory effects of lncRNA SLNCR1 siRNA silencing on cell migration, invasion and stemness. In conclusion, lncRNA SLNCR1 may regulate cancer cell migration, invasion and stemness in NSCLC through interactions with sPLA2.

Overexpression of lncRNA GATA6-AS inhibits cancer cell proliferation in mantle cell lymphoma by downregulating GLUT1.

Long non-coding RNA GATA6 antisense RNA 1 (lncRNA GATA6-AS) is a recently identified lncRNA that is involved in endothelial-mesenchymal transition. The present study aimed to investigate the involvement of GATA6-AS in the progression of mantle cell lymphoma (MCL). It was found that plasma lncRNA GATA6-AS expression level was downregulated in patients with MCL, compared with that in healthy controls. Downregulation of lncRNA GATA6-AS has potential diagnostic value in early stage MCL. Overexpression of lncRNA GATA6-AS resulted in inhibited glucose uptake in the human cell lines JVM-2 and Z-138 MCL. Inhibited expression of glucose transporter 1 (GLUT1) was observed in MCL cells following lncRNA GATA6-AS overexpression, whilst GLUT1 overexpression did not alter the expression of lncRNA GATA6-AS. Additionally, lncRNA GATA6-AS overexpression inhibited, whilst GLUT1 overexpression promoted the proliferation of JVM-2 and Z-138 MCL cells; GLUT1 overexpression partially reversed the inhibitory effects of lncRNA GATA6-AS overexpression. It was therefore concluded that lncRNA GATA6-AS may inhibit cancer cell proliferation in MCL by downregulating GLUT1.

LncRNA NKILA was upregulated in diabetic cardiomyopathy with early prediction values.

Nuclear factor-κB interacting long non-coding RNA (LncRNA NKILA) is a well-studied tumor suppressor lncRNA in several types of malignancies. The present study reports the involvement of this lncRNA in diabetic cardiomyopathy (DC). A 8-year-follow-up study on 312 diabetic patients without exhibiting obvious complications demonstrated that plasma lncRNA NKILA levels were upregulated specifically in diabetic patients who developed DC but not in patients with other complications. Plasma levels of lncRNA NKILA at 6 months prior to diagnosis is sufficient to distinguish patients with DC from other diabetic patients without significant complications. Although in vitro experiments demonstrated that lncRNA NKILA expression in cardiomyocyte cells was not affected by high-glucose treatment, ectopic lncRNA NKILA expression and lncRNA NKILA knockdown potentiated, and inhibited cardiomyocyte apoptosis, respectively. Therefore, the data from the present study suggests that overexpression of lncRNA NKILA is involved in DC, and overexpression of lncRNA NKILA may serve as a therapeutic target for treating DC.

Plasma lncRNA expression profile as a prognostic tool in BRAF-mutant metastatic melanoma patients treated with BRAF inhibitor.

Long non-coding RNAs (lncRNA) are dysregulated in many cancer types. Abnormal baseline levels of these lncRNAs display diagnostic and prognostic potential in cancer patients. The aim of this study was to evaluate the prognostic value of plasma lncRNAs in BRAF-mutant advanced melanoma patients treated with a BRAF inhibitor. Total RNA was isolated from plasma samples collected from 58 advanced BRAF-mutant melanoma patients and 15 healthy donors. The expression levels of 90 lncRNAs were estimated using the LncProfiler qPCR Array Kit (SBI) and LightCycler 96 (Roche). LncRNA expression levels correlated with responses to the BRAF inhibitor (vemurafenib) treatment. The patients were stratified into three groups based on their lncRNA levels with various lncRNA expressions (low, medium, and high). A Cox proportional hazards regression model was used to determine the lncRNAs that were significantly associated with both progression-free and overall survivals (PFS and OS, respectively) in patients receiving vemurafenib. The expression level of 12 lncRNAs was down-regulated, while five lncRNAs were up-regulated in melanoma patients compared to healthy donors. Kaplan-Meier analysis showed that upregulation or downregulation of 11 and 16 different lncRNAs were associated with longer median PFS and OS, respectively. Further analysis demonstrated that the baseline lncRNAs for IGF2AS, anti-Peg11, MEG3, Zeb2NAT are independent prognostic factors in BRAF-mutant advanced melanoma patients treated with vemurafenib. Evaluation of plasma lncRNAs expression level for advanced melanoma diagnosis and prognosis evaluation appears to be a safe and valuable method; however, this method requires further validation in larger cohorts and randomized trials.

Overexpression of Long Noncoding RNAs (lncRNA) NF-κβ-Interacting Long Noncoding RNA (NKILA) in Ankylosing Spondylitis is Correlated with Transforming Growth Factor β1 (TGF-β1), Active Disease and Predicts Length of Treatment.

BackgroundLong noncoding RNAs (lncRNA) NF-κβ-interacting long noncoding RNA (NKILA) is downregulated in various types of cancers, while its involvement in other diseases is unknown. In the present study we found that plasma lncRNA NKILA was expressed at higher levels in active ankylosing spondylitis patients than in healthy controls.Material/MethodsAccording to Youden’s index, active disease patients were divided into high and low lncRNA NKILA groups.ResultsPatients in the high lncRNA NKILA level group had significantly longer length of treatment and higher re-hospitalization rate at 3 years after discharge. Plasma levels of TGF-β1 were also higher in active ankylosing spondylitis patients than in healthy controls. Levels of plasma lncRNA NKILA and TGF-β1 were significantly and positively correlated in ankylosing spondylitis patients but not in healthy controls.ConclusionsOverexpression of lncRNA NKILA in ankylosing spondylitis is correlated with active disease and predicts length of treatment. LncRNA NKILA may participate in ankylosing spondylitis through the interaction with TGF-β1, which is a key player in this disease.

LncRNA DILC is downregulated in osteoarthritis and regulates IL‐6 expression in chondrocytes

Excessive production of interleukin 6 (IL-6) is involved in the pathogenesis of osteoarthritis. It has been reported that long noncoding RNA (lncRNA) DILC inhibited IL-6 to regulate liver cancer stem cells. Therefore, lncRNA DILC may also participate in osteoarthritis. We found that lncRNA DILC was downregulated, while IL-6 was upregulated in plasma of osteoarthritis patients comparing to the control group. Levels of plasma lncRNA DILC and IL-6 were significantly and inversely correlated only in patients with osteoarthritis. Downregulation of lncRNA DILC effectively distinguished patients with osteoarthritis from the control group. Overexpression of lncRNA DILC resulted in inhibited IL-6 expression in chondrocytes, while treatment with exogenous IL-6 did not affect lncRNA DILC expression. However, lncRNA DILC overexpression did not affect the proliferation and apoptosis of chondrocytes. Therefore, lncRNA DILC is downregulated in osteoarthritis and regulates IL-6 expression in chondrocytes.

LncRNA DILC participates in rheumatoid arthritis by inducing apoptosis of fibroblast-like synoviocytes and down-regulating IL-6.

IL-6 produced by human fibroblast-like synoviocytes (HFLS) promotes rheumatoid arthritis (RA), while lncRNA DILC regulates liver cancer stem cells by inhibiting IL-6. Therefore, lncRNA DILC may participate in RA. In the present study, we found that plasma lncRNA DILC was down-regulated, while IL-6 was up-regulated in RA patients than in healthy controls. Plasma levels of lncRNA DILC and IL-6 were significantly and inversely correlated only in RA patients. Overexpression of lncRNA DILC resulted in promoted apoptosis of HFLS isolated from RA patients, while lncRNA DILC siRNA silencing played an opposite role. In addition, overexpression of lncRNA DILC also resulted in inhibited IL-6 expression in HFLS isolated from RA patients. Therefore, lncRNA DILC may participate in RA by inducing apoptosis of HFLS and down-regulating IL-6.

Research on the correlation of changes in plasma lncRNA MEG3 with change in inflammatory factors and prognosis in patients with traumatic brain injury.

To study the correlation between the plasma long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) and the levels of inflammatory cytokines in patients with traumatic brain injury (TBI) and to evaluate its prognosis to screen new biological targets for the diagnosis and treatment of TBI. 40 patients with TBI (TBI group) and 40 healthy people (control group) were collected and venous blood was drawn. The plasma MEG3 in subjects was quantitatively analyzed via quantitative Polymerase Chain Reaction (qPCR). Moreover, the levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-8] in plasma in each group were detected via enzyme-linked immunosorbent assay (ELISA). Finally, the correlation analysis was performed for the MEG3 expression level and inflammatory cytokine levels in patients with TBI. Patients were divided into high-expression MEG3 group and low-expression MEG3 group, high-level inflammatory cytokine group and low-level inflammatory cytokine group according to the median, followed by prognosis evaluation. The MEG3 expression level in TBI group was significantly decreased compared to that in control group, and the levels of inflammatory cytokines in plasma, including TNF-α, IL-1β, IL-6, and IL-8, were significantly higher than in control group. The results of the correlation analysis showed that the expression level of plasma MEG3 had a significantly negative correlation with the level of each inflammatory cytokine. The prognostic analysis revealed that the prognosis of patients with high MEG3 expression level and low inflammatory cytokine levels was good, while it was poor in patients with low MEG3 expression level and high inflammatory cytokine levels; the difference was significant. In patients with TBI, the expression level of plasma MEG3 is decreased, while the inflammatory cytokine levels are increased, and there is a significantly negative correlation between the two items. The prognosis of patients with high MEG3 expression level and low inflammatory cytokine levels is good so MEG3 and inflammatory cytokines can be used as biomarkers for diagnosis and treatment of TBI, improving the prognosis of patients.

LncRNA AWPPH and miRNA-21 regulates cancer cell proliferation and chemosensitivity in triple-negative breast cancer by interacting with each other.

Long-non-coding RNAs (lncRNA) AWPPH promotes the progression of liver and bladder cancer, indicating its oncogenic role. The current study aimed to explore the involvement of AWPPH in triple-negative breast cancer (TNBC). In the current study, we found that plasma levels of lncRNA AWPPH and microRNA-21 (miRNA-21) were upregulated in patients with TNBC than in healthy controls, and the upregulation of plasma lncRNA AWPPH and miRNA-21 distinguished early-stage patients with TNBC from healthy controls. Plasma levels of lncRNA AWPPH and miRNA-21 were significantly and positively correlated in both patients with TNBC and healthy controls. LncRNA AWPPH and miRNA-21 overexpression led to promoted cancer cells proliferation and improved cancer cell viability under carboplatin treatment, while lncRNA AWPPH small interfering RNA (siRNA) silencing played an opposite role. In addition, miRNA-21 overexpression attenuated the effects of lncRNA AWPPH siRNA silencing on of cancer cell behaviors. LncRNA AWPPH overexpression led to upregulated miRNA-21 in TNBC cells, while miRNA-21 overexpression also led to significantly upregulated lncRNA AWPPH expression. Therefore, lncRNA AWPPH and miRNA-21 may regulate cancer cell proliferation and chemosensitivity in TNBC by interacting with each other.

LncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150.

Long noncoding RNAs (lncRNAs) CASC11 is an oncogenic lncRNA in gastric cancer and colorectal cancer. Our study aimed to investigate the role of lncRNA CASC11 in bladder cancer. In this study we showed that plasma lncRNA CASC11 was upregulated, while plasma miRNA‐150 was downregulated in patients with early‐stage bladder cancer than in healthy controls. Altered expression of plasma lncRNA CASC11 and miRNA‐150 separated patients with bladder cancer from healthy controls. lncRNA CASC11 expression was inversely correlated with miRNA‐150 expression in patients with bladder cance but not in healthy controls. Overexpression of lncRNA CASC11 mediated the inhibition of miRNA‐150 expression in cancer cells, while miRNA‐150 overexpression did not significantly alter lncRNA CASC11 expression. lncRNA CASC11 overexpression promoted, while miRNA‐150 overexpression inhibited cancer cell proliferation. miRNA‐150 also attenuated the enhancing effects of lncRNA CASC11 overexpression on cancer cell proliferation. However, overexpression of lncRNA CASC11 showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA CASC11 may promote cancer cell proliferation in bladder cancer, and the actions of lncRNA CASC11 are likely through miRNA‐150.

Plasma Long Non-Coding RNA Expression Profiles in Patients with Rheumatoid Arthritis.

Recently, long non-coding RNAs (lncRNAs) have attracted substantial attention owing to their unforeseen critical roles in a wide range of biological processes. The aim of our study was to provide an overview of lncRNA expression profiles in plasma of RA patients. The Agilent LncRNA + mRNA Human Gene Expression Microarray V4.0 was employed to determine differentially expressed (DE) lncRNAs and mRNAs in plasma of four female newly diagnosed and DMARD-naïve RA patients and four female age-matched healthy controls. The KOBAS (KEGG Orthology Based Annotation System) software was applied to determine the gene ontology (GO) terms and pathway in which the DE mRNAs were enriched. Furthermore, a lncRNA-mRNA co-expression network was constructed according to the correlation between DE lncRNAs and mRNAs. Compared with healthy controls, a total of 289 DE lncRNAs (169 up-regulated and 120 down-regulated) and 468 DE mRNAs (280 up-regulated and 188 down-regulated) were found in the plasma of patients with RA. Bioinformatics analysis indicated that the DE mRNAs might be involved in the pathogenesis of RA mainly through platelets. In addition, a co-expression network composed of 229 network nodes and 340 connections between 116 lncRNAs and 113 mRNAs was constructed. We characterized the plasma lncRNA expression profiles in RA patients for the first time. Our results could shed new light on the pathogenesis of RA and help identify lncRNAs as novel diagnostic biomarkers and therapeutic targets for RA.

Long noncoding RNA HAND2-AS1 inhibits cancer cell proliferation, migration, and invasion in esophagus squamous cell carcinoma by regulating microRNA-21.

Long noncoding RNA (lncRNA) HAND2-AS1 is a well-characterized tumor suppressor in several types of malignancies, while its role in esophagus squamous cell carcinoma (ESCC) is unknown. In this study, we found that lncRNA HAND2-AS1 was downregulated, while microRNA-21 ( miRNA-21) was upregulated in tumor tissues than in adjacent healthy tissues of ESCC patients. Expression levels of lncRNA HAND2-AS1 and miRNA-21 were significantly and inversely correlated in tumor tissues but not in healthy tissues. Plasma levels of lncRNA HAND2-AS1 were lower in ESCC patients than in healthy controls, and downregulation of plasma lncRNA HAND2-AS1 distinguished early stage ESCC patients from healthy controls. lncRNA HAND2-AS1 overexpression resulted in downregulation of miRNA-21 in cells of ESCC cell lines and inhibited cell proliferation, migration, and invasion. miRNA-21 overexpression failed to affect lncRNA HAND2-AS1 expression but significantly attenuated the inhibitory effect of lncRNA HAND2-AS1 overexpression on cancer cell proliferation, migration, and invasion. Therefore, lncRNA HAND2-AS1 may inhibit cancer cell proliferation, migration, and invasion in ESCC by regulating miRNA-21.

LncRNA CASC2 expression is down- regulated in papillary thyroid cancer and promotes cell invasion by affecting EMT pathway.

Long non-coding RNAs (lncRNAs) were recently identified as crucial regulators of papillary thyroid cancer (PTC). However, the clinical role and regulatory functions of lncRNA cancer susceptibility candidate 2 (CASC2) in PTC remain unknown. LncRNA CASC2 expression was examined in plasma samples from 68 PTC patients and 39 patients with nodular goiter (NG). Cell proliferation, migration and invasion abilities were evaluated using CCK8 assay and transwell migration and invasion assay. QRT-PCR and western blot analysis were performed to detect the expression of epithelial-to-mesenchymal (EMT) markers ZEB1, E-cadherin and vimentin in PTC cells. We demonstrated that lncRNA CASC2 expression was significantly downregulated in tumor tissues and plasma samples in patients with PTC compared with those in nodular goiters (P< 0.05). Decreased plasma lncRNA CASC2 expression associated with lymph node metastasis (LNM) of PTC patients and was identified as an independent risk for patients with LNM (P< 0.05). Furthermore, functional assays demonstrated that overexpression of lncRNA CASC2 inhibited cell proliferation, migration and invasion of PTC. Moreover, we demonstrated that overexpression of lncRNA CASC2 suppressed cell epithelial-mesenchymal transition (EMT) process of PTC by increasing the E-cadherin expression, but downregulating ZEB1 and N-cadherin expression. Thus, these results indicated that lncRNA CASC2 was a predictor for LNM of PTC patients and may serve as a potential target of PTC treatment.

A Plasma Long Noncoding RNA Signature for Early Detection of Lung Cancer

The early detection of lung cancer is a major clinical challenge. Long noncoding RNAs (lncRNAs) have important functions in tumorigenesis. Plasma lncRNAs directly released from primary tumors or the circulating cancer cells might provide cell-free cancer biomarkers. The objective of this study was to investigate whether the lncRNAs could be used as plasma biomarkers for early-stage lung cancer. By using droplet digital polymerase chain reaction, we determined the diagnostic performance of 26 lung cancer–associated lncRNAs in plasma of a development cohort of 63 lung cancer patients and 33 cancer-free individuals, and a validation cohort of 39 lung cancer patients and 28 controls. In the development cohort, 7 of the 26 lncRNAs were reliably measured in plasma. Two (SNHG1 and RMRP) displayed a considerably high plasma level in lung cancer patients vs. cancer-free controls (all P < .001). Combined use of the plasma lncRNAs as a biomarker signature produced 84.13% sensitivity and 87.88% specificity for diagnosis of lung cancer, independent of stage and histological type of lung tumor, and patients' age and sex (all P > .05). The diagnostic value of the plasma lncRNA signature for lung cancer early detection was confirmed in the validation cohort. The plasma lncRNA signature may provide a potential blood-based assay for diagnosing lung cancer at the early stage. Nevertheless, a prospective study is warranted to validate its clinical value.

Circulating long noncoding RNA DKFZP434I0714 predicts adverse cardiovascular outcomes in patients with end-stage renal disease

BackgroundCardiovascular (CV) diseases are major causes of mortality in uremic patients. Conventional risk factors fail to identify uremic patients with increased propensity for adverse CV outcomes. We aimed to test the hypothesis that circulating long noncoding RNAs (lncRNAs) could be a prognostic marker to predict adverse CV outcomes in uremic patients. Methods and resultsPlasma lncRNAs were profiled in patients with end-stage renal disease (ESRD, n = 28) or chronic kidney disease (CKD, n = 8) and in healthy (n = 12) subjects by RNA sequencing. A total of 179 lncRNAs were significantly dysregulated with ESRD; the expression signature of plasma lncRNAs distinguished ESRD from both CKD and control samples. Analysis on a microarray dataset obtained from renal biopsy samples of patients with advanced kidney disease (GSE66494) revealed that a significant proportion of plasma lncRNAs (30.7%) and mRNAs (49.5%) dysregulated with uremia were similarly dysregulated in diseased kidneys, suggesting that plasma RNA profiles mirror the transcriptomal changes in diseased kidney tissues. Further analyses identified eight plasma lncRNAs as potential predictors of adverse CV outcomes in uremic patients. Validation study in an independent cohort of ESRD patients (n = 111) confirmed that elevated plasma lncRNA DKFZP434I0714 is a significant independent predictor of adverse CV outcomes in uremic patients. Additional experiments demonstrated the functional involvement of DKFZP434I0714 in the pathogenesis of endothelial dysfunction. ConclusionsIn summary, plasma lncRNA expression signature reflects the disease states of uremia. Elevated plasma levels of lncRNA DKFZP434I0714 in uremic patients portend a worse CV outcome and warrant closer monitoring and more aggressive management.

Circulating long noncoding RNA ANRIL downregulation correlates with increased risk, higher disease severity and elevated pro-inflammatory cytokines in patients with acute ischemic stroke.

To investigate the correlation of plasma lncRNA ANRIL expression with stroke risk, severity and inflammatory cytokines levels in acute ischemic stroke (AIS) patients. A total of 126 AIS patients and 125 controls were consecutively recruited in this case-control study. Blood samples from all participants were collected, and plasma was separated. Plasma lncRNA ANRIL expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Plasma tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β (IL-1β), IL-6, IL-8, IL-10, and IL-17 levels were measured by enzyme-linked immunosorbent assay (ELISA). National Institutes of Health Stroke Scale (NIHSS) scores were used to assess the stroke severity in AIS patients. Plasma lncRNA ANRIL expression was lower in AIS patients than in controls (P<0.001), and the receiver operating characteristic (ROC) curve showed a good prediction value of lncRNA ANRIL for AIS risk with area under curve (AUC) of 0.759 (95% CI: 0.741-0.849). In addition, lncRNA ANRIL expression was negatively correlated with NIHSS score (r=-0.351, P<0.001). Furthermore, while lncRNA ANRIL expression was negatively associated with hs-CRP level (r=-0.247, P=0.005), no correlation was found between lncRNA ANRIL expression and ESR level (P=0.619). For inflammatory cytokines, lncRNA ANRIL expression was inversely associated with TNF-α (r=-0.216, P=0.015) and IL-6 levels (r=-0.326, P<0.001), while it positively correlated with IL-10 level (r=0.210, P=0.018). Circulating lncRNA ANRIL downregulation correlates with increased stroke risk, higher disease severity and elevated inflammation in AIS patients.

LncRNA snaR upregulates GRB2-associated binding protein 2 and promotes proliferation of ovarian carcinoma cells

BackgroundThe functionality of lncRNA snaR has only been characterized in breast cancer and colon cancer. The aim of the current study is to explore the involvement of lncRNA snaR in ovarian carcinoma (OC). Materials and methodsExpression of lncRNA snaR and GRB2-associated binding protein 2 (GAB2) in plasma of both patients with OC and healthy females was detected by qRT-PCR. Application value of plasma lncRNA snaR in the diagnosis of OC was evaluated by ROC analysis. Correlation between plasma lncRNA snaR and GAB2 was analyzed by Pearson correlation coefficient. LncRNA snaR and GAB2 expression vectors as well as GAB2 siRNA were transfected into cells of human OC cell lines, and the effect on lncRNA snaR expression, GAB2 expression and cell proliferation was detected by qRT-PCR, western blot and CCK-8 assay. ResultsIt was observed that plasma levels of lncRNA snaR and GAB2 were significantly higher in OC patients than those in healthy controls. In effect, high levels of plasma lncRNA snaR and GAB2 distinguished OC patients from healthy controls. Plasma lncRNA snaR and GAB2 were positively correlated in OC patients but not in healthy controls. LncRNA snaR overexpression promoted cancer cell proliferation and upregulated GAB2 expression. ConclusionsGAB2 overexpression also promoted cancer cell proliferation but showed no significant effects on lncRNA snaR expression, while GAB2 siRNA silencing significantly attenuated the enhancing effects of lncRNA snaR overexpression on cancer cell proliferation. LncRNA snaR may promote proliferation of ovarian carcinoma cells by upregulating GAB2 expression.

Diagnostic utility of plasma lncRNA small nucleolar RNA host gene 1 in patients with hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) offer great potential as cancer biomarkers. Owing to the limited sensitivity and specificity of α-fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma (HCC), the present study used an lncRNA microarray to screen aberrantly expressed lncRNAs in HCC tissues. Subsequently, the expression profile of the target lncRNAs was investigated in plasma from patients with HCC or hepatitis B virus-positive chronic hepatitis and cirrhosis (HCH), as well as from healthy volunteers. A total of six aberrantly expressed lncRNAs were identified in HCC tissues and corresponding normal tissues, from which only small nucleolar RNA host gene 1 (SNHG1) expression in HCC tissues demonstrated a good correlation with those in plasma from HCC patients. Subsequent analysis revealed that high plasma SNHG1 expression levels were correlated with tumor size, TNM stage and AFP levels. Receiver operating characteristic analysis demonstrated that SNHG1 yields an excellent diagnostic ability to differentiate between patients with HCC and unaffected control patients, which was superior to that of AFP. The combination of SNHG1 with AFP may be able to distinguish HCC from HCH or healthy volunteers with the area under the curve values of 0.86 and 0.97, respectively. In summary, it was demonstrated that plasma SNHG1 has great potential as a sensitive and reliable biomarker for the diagnosis of HCC.

Circulating lncRNA IFNG-AS1 expression correlates with increased disease risk, higher disease severity and elevated inflammation in patients with coronary artery disease.

This study aimed to investigate the associations of circulating long, non-coding (lncRNA) IFNG-AS1, lncRNA ANRIL and lncRNA ITSN1 relative expressions with disease risk, severity and inflammatory cytokines levels in coronary artery disease (CAD) patients. One hundred and ninety-one patients suspected of CAD who underwent coronary angiography were consecutively enrolled in this casecontrol study, and divided into CAD patients (N=102) and controls (N=89) according to coronary angiographic results. Blood samples of all participants were collected. Plasma lncRNA IFNG-AS1, lncRNA ANRIL and lncRNA ITSN1 expressions were detected using quantitative polymerase chain reaction (qPCR). Serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β (IL-1β), IL-6, IL-8, IL-10, and IL-17 were assessed using enzyme-linked immunosorbent assay (ELISA). Gensini Score was used to evaluate the disease severity of CAD patients. LncRNA IFNG-AS1 relative expression in CAD patients was upregulated compared with that in controls (P<.001), and the receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of lncRNA-IFNG-AS1 for predicting the risk of CAD was 0.755 (95% CI: 0.688-0.821). lncRNA IFNG-AS1 relative expression was remarkably associated with Gensini Score (r=.259, P=.009). Additionally, lncRNA IFNG-AS1 relative expression was positively associated with high-sensitivity C-reactive protein (hs-CRP) (r=.283, P=.004), TNF-α (r=.269, P=.006), and IL-6 levels (r=.425, P<.001), while it was negatively correlated with IL-10 level (r=-.263, P=.008). lncRNA ANRIL or lncRNA ITSN1 was not correlated with CA D risk, Gensini Score, hs-CRP, ESR, TNF-α, IL-1β, IL-6, IL-8, IL-10, or IL-17 levels (all P>.05). Circulating lncRNA IFNG-AS1 expression correlates with increased disease risk, higher disease severity and elevated inflammation in CAD patients.