Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism.

We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder.

Expression of polycystins and fibrocystin on primary cilia of lung cells.

Mutations in polycystin-1, polycystin-2, or fibrocystin account for autosomal dominant or recessive polycystic kidney disease. Renal cystogenesis is linked to abnormal localization and function of these cystoproteins in renal primary cilia. They are also expressed in extrarenal tissues in which their functions are unclear. Here we found that human type-II alveolar epithelial A549, airway submucosal Calu-3 cells, and rat bronchioles contain primary or multiple cilia in which we detected these cystoproteins. At sub-confluency, polycystin-1 was expressed on plasma membrane, while polycystin-2 was localized to the ER of resting cells. Both polycystins were detected on the spindle and mid-body of mitotic cells, while fibrocystin was on centrosome throughout cell cycle. Polycystins and fibrocystin may participate in regulating mucociliary sensing and transport within pulmonary airways.

Association between serum free fatty acid levels and possible related factors in patients with type 2 diabetes mellitus and acute myocardial infarction.

BACKGROUND: Free fatty acids (FFAs) play importance roles in the development of diabetes and cardiovascular diseases. We measured serum FFA levels from type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI) patients and assay the correlation between serum FFA levels and related factors. The present study was undertaken to investigate a possible relation between the changes in serum free fatty acid concentration with acute myocardial infarction and type 2 diabetes mellitus. METHODS: The study population consisted of 540 healthy individuals and 103 patients with T2DM, 59 patients with AMI and 21 volunteers. Serum FFAs were measured with high pressure liquid chromatography. Blood urea nitrogen and uric acid were measured in clinical laboratory, as were glycemic, lipid and blood routine parameters. We selected 242 individuals with age over 60 years, 143 healthy individuals and 52 patients with T2DM, 47 patients with AMI were incorporated into three groups as control group, T2DM group and AMI group. Associations were analyzed with stepwise regression analysis with adjusted for age, sex, body mass index. RESULTS: Serum FFA levels were significantly higher in the age over 60 years individuals compared to 20 ~ 50 years (logFFA µmmol/L:2.60 ± 0.16 vs. 2.73 ± 0.18, P < .001) in the healthy group. We found lower FFA levels in the AMI compared to the T2DM and control group (2.64 ± 0.22 vs. 2.72 ± 0.13&2.72 ± 0.16, respectively, P < .05&P < 0.01) in the age over 60, fasting blood glucose level higher in the AMI and T2DM (5.78 ± 1.32&7.75 ± 2.93 mmol/L vs. 4.90 ± 0.47 mmol/L, P < .01&P < .001) compared with the normal group, HDL level (1.01 ± 0.22&0.98 ± 0.18 mmol/L vs.1.30 ± 0.22 mmol/L, P < .001&P < .001). With stepwise regression analysis, the serum FFA levels was positively associated with the HDL in the control group (YlogFFA = 2.32 + 0.33XHDL, R = 0.26, P < .01) and T2MD (YlogFFA = 2.46 + 0.27XHDL, R = 0.36, P < .05), AST in AMI (YlogFFA =2.24 + 0. 015XAST, R = 0.49, P < .01). CONCLUSIONS: Compared to control group, serum FFA levels were decreased only in AMI group, while HDL level was increased in both AMI and T2DM group. The serum FFA levels were positive association with the HDL level in both T2DM and control group, FFA levels were positive association with AST in AMI.

Diagnostic potential of differentially expressed Homer1, IL-1ß, and TNF-α in coronary artery disease.

Increasing evidences suggest that inflammation plays an important role in the pathogenesis of coronary artery disease (CAD). Numerous inflammatory cytokines and related genes mediate adverse cardiovascular events in patients with CAD, such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and Homer in the present study. The study was carried out on 163 CAD patients at different stages and 68 controls. The gene expression of Homer1, Homer2, Homer3, IL-1ß, and TNF-α in the peripheral blood leukocytes were measured by real-time polymerase chain reaction. The mRNA levels of Homer1, IL-1ß, and TNF-α in CAD patients were significantly higher than those in the control group, but not Homer2 and Homer3. However, there was no considerable difference in the mRNA levels of Homer1, IL-1ß, and TNF-α among AMI, UAP, and SAP three subgroups of CAD. The receiver operating characteristic (ROC) curves showed that Homer1 had a better diagnostic value for UAP patients compared with IL-1ß and TNF-α. Like IL-1ß and TNF-α, Homer1 may also be an important participant of atherosclerotic plaque development and eventually rupture. The results of the present study may provide an important basis for diagnosing CAD patients, and provide new therapeutic targets for CAD.

Receptor for activated C kinase 1 (RACK1) inhibits function of transient receptor potential (TRP)-type channel Pkd2L1 through physical interaction.

Pkd2L1 (also called TRPP3) is a non-selective cation channel permeable to Ca(2+), Na(+), and K(+) and is activated by Ca(2+). It is also part of an acid-triggered off-response cation channel complex. We previously reported roles of the Pkd2L1 C-terminal fragments in its channel function, but the role of the N terminus remains unclear. Using a yeast two-hybrid screening, we found that the Pkd2L1 N terminus interacts with the receptor for activated C kinase 1 (RACK1), a scaffolding/anchoring protein implicated in various cellular functions. This interaction requires the last two Trp-Asp (WD) motifs of RACK1 and fragment Ala(19)-Pro(45) of Pkd2L1. The interaction was confirmed by GST pulldown, blot overlay, and co-immunoprecipitation assays. By (45)Ca tracer uptake and two-microelectrode voltage clamp electrophysiology, we found that in Xenopus oocytes with RACK1 overexpression Pkd2L1 channel activity is abolished or substantially reduced. Combining with oocyte surface biotinylation experiments, we demonstrated that RACK1 inhibits the function of Pkd2L1 channel on the plasma membrane in addition to reducing its total and plasma membrane expression. Overexpressing Pkd2L1 N- or C-terminal fragments as potential blocking peptides for the Pkd2L1-RACK1 interaction, we found that Pkd2L1 N-terminal fragment Met(1)-Pro(45), but not Ile(40)-Ile(97) or C-terminal fragments, abolishes the inhibition of Pkd2L1 channel by overexpressed and oocyte-native RACK1 likely through disrupting the Pkd2L1-RACK1 association. Taken together, our study demonstrated that RACK1 inhibits Pkd2L1 channel function through binding to domain Met(1)-Pro(45) of Pkd2L1. Thus, Pkd2L1 is a novel target channel whose function is regulated by the versatile scaffolding protein RACK1.

FKBP11 upregulation promotes proliferation and migration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths world over. Early diagnosis and effective treatment monitoring significantly improves patients' outcomes. FKBP11 gene is highly expressed in HCC and could play a role in its development, early diagnosis and treatment. OBJECTIVE: This study aimed to evaluate the expression of FKBP11 in HCC, its correlation with patients' clinical characteristics and potential role in HCC development. METHODS: Expression was determined by bioinformatics analysis, quantitative real-time PCR, western blot, and immunohistochemistry. CCK-8, Transwell and wound healing assays were used to investigate involvement in HCC development. RESULTS: FKBP11 was significantly upregulated in HCC cells, tissues and blood (all p< 0.001). Its receiver operator characteristic (ROC) curve had an AUC of 0.864 (95% CI: 0.823-0.904), at a sensitivity of 0.86 and specificity of 0.78 indicating a good diagnostic potential in HCC. Its expression was markedly reduced after surgery (p< 0.0001), indicating a potential application in HCC treatment follow-up. Knockdown of FKBP11 in HCC cells attenuated proliferation and migration, suggesting a possible role in HCC pathogenesis. CONCLUSION: This study thus found that FKBP11 is upregulated in HCC, and the upregulation promotes HCC development. FKBP11 levels are significantly reduced post-surgery and could be a potential diagnostic and prognostic marker for HCC.

Neuronal activity regulates glutamate transporter dynamics in developing astrocytes.

Glutamate transporters (GluTs) maintain a low ambient level of glutamate in the central nervous system (CNS) and shape the activation of glutamate receptors at synapses. Nevertheless, the mechanisms that regulate the trafficking and localization of transporters near sites of glutamate release are poorly understood. Here, we examined the subcellular distribution and dynamic remodeling of the predominant GluT GLT-1 (excitatory amino acid transporter 2, EAAT2) in developing hippocampal astrocytes. Immunolabeling revealed that endogenous GLT-1 is concentrated into discrete clusters along branches of developing astrocytes that were apposed preferentially to synapsin-1 positive synapses. Green fluorescent protein (GFP)-GLT-1 fusion proteins expressed in astrocytes also formed distinct clusters that lined the edges of astrocyte processes, as well as the tips of filopodia and spine-like structures. Time-lapse three-dimensional confocal imaging in tissue slices revealed that GFP-GLT-1 clusters were dynamically remodeled on a timescale of minutes. Some transporter clusters moved within developing astrocyte branches as filopodia extended and retracted, while others maintained stable positions at the tips of spine-like structures. Blockade of neuronal activity with tetrodotoxin reduced both the density and perisynaptic localization of GLT-1 clusters. Conversely, enhancement of neuronal activity increased the size of GLT-1 clusters and their proximity to synapses. Together, these findings indicate that neuronal activity influences both the organization of GluTs in developing astrocyte membranes and their position relative to synapses.

Upregulation of the long non-coding RNA, LIPCAR promotes proliferation, migration, and metastasis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) early diagnosis remains a challenge to date. Alpha-feto protein, though less sensitive remains widely used for both diagnosis and prognosis. Recently however, a number of molecular biomarkers have been suggested as alternatives to Alpha feto protein, especially for early diagnosis. OBJECTIVE: To determine the role of the long non-coding RNA, LIPCAR in the pathogenesis and early diagnosis of hepatocellular carcinoma. METHODS: Quantitative real-time PCR, and Fluorescence in situ hybridization assays were conducted to determine LIPCAR expression in HCC vs normal blood samples, and HCC cell lines vs normal liver cell lines. Transfection was done to upregulate LIPCAR in one HCC cell line, and used to study cell proliferation, migration, apoptosis and epithelial-mesenchymal transformation. Animal experiment was finally done to determine its effect on metastasis. RESULTS: LIPCAR was significantly upregulated in HCC blood samples and HCC cell lines compared to their respective normal ones. Its overexpression promoted hepatocellular carcinoma cell proliferation, and migration, while inhibiting apoptosis. Its overexpression also promoted epithelial-mesenchymal transformation in hepatocellular carcinoma cells, and metastasis in vivo. CONCLUSION: The study demonstrated that the lncRNA, LIPCAR is significantly upregulated in hepatocellular carcinoma patients and that its upregulation promotes HCC proliferation, migration, and metastases.

Network pharmacology and RNA-sequencing reveal the molecular mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Up to 20%-30% of patients hospitalized with COVID-19 have evidence of cardiac dysfunction. Xuebijing injection is a compound injection containing five traditional Chinese medicine ingredients, which can protect cells from SARS-CoV-2-induced cell death and improve cardiac function. However, the specific protective mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction remains unclear. METHODS: The therapeutic effect of Xuebijing injection on COVID-19 was validated by the TCM Anti COVID-19 (TCMATCOV) platform. RNA-sequencing (RNA-seq) data from GSE150392 was used to find differentially expressed genes (DEGs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. Data from GSE151879 was used to verify the expression of Angiotensin I Converting Enzyme 2 (ACE2) and central hub genes in both human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) and adult human CMs with SARS-CoV-2 infection. RESULTS: A total of 97 proteins were identified as the therapeutic targets of Xuebijing injection for COVID-19. There were 22 DEGs in SARS-CoV-2 infected hiPSC-CMs overlapped with the 97 therapeutic targets, which might be the therapeutic targets of Xuebijing injection on COVID-19-induced cardiac dysfunction. Based on the bioinformatics analysis, 7 genes (CCL2, CXCL8, FOS, IFNB1, IL-1A, IL-1B, SERPINE1) were identified as central hub genes and enriched in pathways including cytokines, inflammation, cell senescence and oxidative stress. ACE2, the receptor of SARS-CoV-2, and the 7 central hub genes were differentially expressed in at least two kinds of SARS-CoV-2 infected CMs. Besides, FOS and quercetin exhibited the tightest binding by molecular docking analysis. CONCLUSION: Our study indicated the underlying protective effect of Xuebijing injection on COVID-19, especially on COVID19-induced cardiac dysfunction, which provided the theoretical basis for exploring the potential protective mechanism of Xuebijing injection on COVID19-induced cardiac dysfunction.

Long non-coding SNHG1 in cancer.

OBJECTIVES: Long non-coding RNAs (lncRNAs) consist of a cluster of RNAs having >200 nucleotides lacking protein-coding function. Recent studies indicate that lncRNAs are involved in various cellular processes and their aberrant expression may lead to tumour development and progression. They may also serve as oncogenes or tumour suppressor genes in other diseases. In this review, we emphasize current investigations involving clinical management, tumour progression and the molecular mechanism of SNHG1 in human cancer. MATERIALS AND METHODS: We investigate and summarize recent studies regarding the biologic functions and mechanisms of lncRNA SNHG1 in tumorigenesis. Related studies were obtained through a systematic search of google scholar, PubMed, Embase and Cochrane Library. RESULTS: SNHG1 is a novel oncogenic lncRNA aberrantly expressed in different diseases including colorectal, liver, lung, prostate, gastric and esophageal cancers as well as ischemic stroke, nasopharyngeal carcinoma, laryngeal squamous cell carcinoma, neuroblastoma, renal cell carcinoma and osteosarcoma. Upregulation of SNHG1 was significantly associated with advanced tumour stage, tumour size, TNM stage and decreased overall survival. Furthermore, aberrant expression of SNHG1 contributes to cell proliferation, metastasis, migration and invasion of cancer cells. CONCLUSION: SNHG1 likely acts as a useful tumour biomarker for cancer diagnosis, prognosis and treatment.

Role of BCYRN1 in hepatocellular carcinoma pathogenesis by lncRNA-miRNA-mRNA network analysis and its diagnostic and prognostic value.

Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results:BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA-miRNA-mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.

TGF-ß1 and TNF-α synergistically induce epithelial to mesenchymal transition of breast cancer cells by enhancing TAK1 activation.

TGF-ß1 is a main inducer of epithelial to mesenchymal transition (EMT). However, many breast cancer cells are not sensitive to the EMT induction by TGF-ß1 alone. So far, the mechanisms underlying the induction of TGF-ß1-insensitive breast cancer cells remains unclear. Here we report that TNF-α can induce EMT and invasiveness of breast cancer cells which are insensitive to TGF-ß1. Intriguingly, TGF-ß1 could cooperate with TNF-α to promote the EMT and invasiveness of breast cancer cells. The prolonged co-stimulation with TGF-ß1 and TNF-α could enhance the sustained activation of Smad2/3, p38 MAPK, ERK, JNK and NF-κB pathways by enhancing the activation of TAK1, which was mediated by the gradually up-regulated TßRs. Except for JNK, all of these pathways were required for the effects of TGF-ß1 and TNF-α. Importantly, the activation of p38 MAPK and ERK pathways resulted in a positive feed-back effect on TAK1 activation by up-regulating the expression of TßRs, favoring the activation of multiple signaling pathways. Moreover, SLUG was up-regulated and required for the TGF-ß1/TNF-α-induced EMT and invasiveness. In addition, SLUG could also enhance the activation of signaling pathways by promoting TßRII expression. These findings suggest that the up-regulation of TßRs contributes to the sustained activation of TAK1 induced by TGF-ß1/TNF-α and the following activation of multiple signaling pathways, resulting in EMT and invasiveness of breast cancer cells.

TNFSF15 is likely a susceptibility gene for systemic lupus erythematosus.

We aim to explore the correlation of TNFSF15 genetic polymorphisms with susceptibility to systemic lupus erythematosus (SLE). This study enrolled SLE patients and healthy individuals to detect three single nucleotide polymorphisms (SNPs) of TNFSF15 (rs3810936, rs6478108 and rs4979462) through using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze the possible association of these three SNPs with the risk of SLE and the mRNA level of TNFSF15 was quantified by real-time PCR. The rs3810936 T allele carrier greatly decreased risk of SLE (OR = 0.620, 95% CI = 0.454-0.849, P = 0.003), while the risk of SLE for rs4979462 T allele carrier was significantly increased (OR = 1.66, 95% CI = 1.243-2.218, P < 0.001). The mRNA level of TNFSF15 was obviously higher in SLE patients, and specifically, the patients who carried the CC genotype of TNFSF15 rs3810936 had a higher TNFSF15 mRNA, but the rs4979462 CC genotype carriers appeared to be associated with the decreased TNFSF15 mRNA (all P < 0.05). Besides, the genotypes of rs3810936 and rs4979462 of TNFSF15 were significantly associated with butterfly rash, arthritis, serositis, renal nephritis, hematological disorder, immunological disorder and positive antinuclear antibody (ANA) of SLE patients (all P < 0.05). CCT and CTT haplotypes were risk factors of SLE, but CCC and TTT were protective factors of SLE (all P < 0.05). Logistic regression analysis showed that rs3810936 and rs4979462 of TNFSF15, histories of chilblain and wet living environment were independently associated with the risk of SLE (all P < 0.05).The current results suggested that TNFSF15 (rs3810936 and rs4979462) SNPs may confer susceptibility to SLE risk, which were significantly associated with the clinical phenotypes of SLE.

LncRNA-DANCR: A valuable cancer related long non-coding RNA for human cancers.

OBJECTIVES: Long noncoding RNAs (lncRNA) are a type of noncoding RNA that comprise of longer than 200 nucleotides sequences. They can regulate chromosome structure, gene expression and play an essential role in the pathophysiology of human diseases, especially in tumorigenesis and progression. Nowadays, they are being targeted as potential biomarkers for various cancer types. And many research studies have proven that lncRNAs might bring a new era to cancer diagnosis and support treatment management. The purpose of this review was to inspect the molecular mechanism and clinical significance of long non-coding RNA- differentiation antagonizing nonprotein coding RNA(DANCR) in various types of human cancers. MATERIALS AND METHODS: In this review, we summarize and figure out recent research studies concerning the expression and biological mechanisms of lncRNA-DANCR in tumour development. The related studies were obtained through a systematic search of PubMed, Embase and Cochrane Library. RESULTS: Long non-coding RNAs-DANCR is a valuable cancer-related lncRNA that its dysregulated expression was found in a variety of malignancies, including hepatocellular carcinoma, breast cancer, glioma, colorectal cancer, gastric cancer, and lung cancer. The aberrant expressions of DANCR have been shown to contribute to proliferation, migration and invasion of cancer cells. CONCLUSIONS: Long non-coding RNAs-DANCR likely serves as a useful disease biomarker or therapeutic cancer target.

Small Nucleolar RNA Host Gene 18 Acts as a Tumor Suppressor and a Diagnostic Indicator in Hepatocellular Carcinoma.

BACKGROUND: Noncoding RNAs are crucial regulators acting as either tumor suppressor genes or oncogenes in human cancer progression. The aberrant expression of noncoding RNAs has been confirmed in different kinds of cancers. Hepatocellular carcinoma is one of the most common malignant tumors worldwide, characterized by insidious onset, great malignancy, and high rates of recurrence and metastasis. Due to lack of early predictive markers, numerous patients are diagnosed in the late stages. As therapeutic options for advanced patients are quite limited, great efforts have been made to screen patients at early stages. A previous study reported that small nucleolar RNA host gene 18 played crucial role in glioma. However, its functions and roles in hepatocellular carcinoma are unknown. PURPOSE: To explore its functional role and diagnostic value in hepatocellular carcinoma, we investigated its expression level. METHODS: We performed real-time quantitative polymerase chain reaction in tumor tissues and adjacent noncancerous tissues derived from patients with hepatocellular carcinoma as well as in plasma, including samples from the healthy control, patients with hepatitis B, cirrhosis, and hepatocellular carcinoma. RESULTS: Small nucleolar RNA host gene 18 was downregulated in liver tissues compared to paired adjacent noncancerous tissues ( P < .0001). Meanwhile, plasma small nucleolar RNA host gene 18 showed a relatively high sensitivity and specificity (75.61% and 73.49%) for distinguishing patients with hepatocellular carcinoma whose α-fetoprotein levels were below 200 ng/mL from the healthy controls. CONCLUSION: Our study suggested that small nucleolar RNA host gene 18 might act as a tumor suppressor gene in hepatocellular carcinoma and potentially a diagnostic indicator to distinguish hepatocellular carcinoma from the healthy control and cirrhosis.

Optical detection of plasma chitotriosidase activity in healthy Chinese children using fluorescence spectrophotometry.

BACKGROUND: Plasma chitotriosidase had been proposed as a biochemical marker of macrophage accumulation in several lysosomal storage disorders. The selection of wavelength and possible interferences and errors have not yet been explored in the assay of chitotriosidase activity. We evaluated the feasibility of measurement of plasma chitotriosidase activity by fluorescence spectrophotometry and established pediatric reference values for earlier diagnosis of related diseases. METHODS: We assayed plasma chitotriosidase activity in 104 healthy Chinese children by a fluorometric approach which combines 3-dimension scan spectra, wavelength scan spectra, time scan spectra and fluorescence intensity analysis. RESULTS: The optimal excitation wavelength and emission wavelength were 358 and 448 nm, respectively. A change of enzyme activity over time was observed fluorometrically, The reference value was 13.04+/-4.94 nmol/ml/h (12.45+/-4.37 nmol/ml/h for boys and 14.04+/-3.99 nmol/ml/h for girls). CONCLUSIONS: We present an integrated application of the fluorescence spectrophotometry as an ideal tool to determine enzymatic activity with 4-methylumbelliferyl triacetylchitotrioside as labeled substrates in clinical laboratory. The function of 3D scan was proved powerful in determination of plasma chitotriosidase activity. The establishment of plasma chitotriosidase activity reference pediatric values was potentially useful for the evaluation of all related diseases.

Decreased expression of LncRNA SRA1 in hepatocellular carcinoma and its clinical significance.

BACKGROUND: Hepatocellular carcinoma (HCC), is an extremely aggressive malignancy with poor prognosis and high fatality rates worldwide. Accumulating evidence indicated that novel biomarkers are required to get a better understanding of the biological mechanisms of HCC. SRA1, a long non-coding RNA (lncRNA), serves as a critical regulator in several cancers. However, the association between SRA1 expression and tumorigenesis in HCC tissues remains unclear. OBJECTIVE: In the present study, we evaluated the expression of SRA1 in HCC and its clinical association. METHODS: The expression levels of SRA1 in 67 pairs of cancer tissues and adjacent normal tissues from HCC patients were detected using quantitative real-time PCR. Expression of SRA1 in HCC cell lines compared with normal human hepatocyte cell lines was also measured. Finally, the potential associations between its level in HCC tissues and the clinicopathological parameters were analyzed as well. RESULTS: The results indicated that the expression levels of SRA1 in HCC were remarkably decreased, compared with matched normal tissues (P< 0.001). Levels of SRA1 in HCC cell lines were also significantly decreased than that in normal human hepatocyte cell line L-02. Additionally, the levels of SRA1 were significantly associated with tumor size (P= 0.020) and serum GLU level (P= 0.046). CONCLUSIONS: This study highlighted that SRA1 was downregulated in HCC and might serve as a tumor suppressor in HCC, which laid a solid foundation for future research.

Prognostic value of abnormally expressed lncRNAs in ovarian carcinoma: a systematic review and meta-analysis.

Ovarian cancer (OC) is the most deadly gynecological cancer and it is urgently needed to find a new marker for the progress of OC. Many long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in ovarian carcinoma, and may serve as prognostic markers. Therefore, we conducted this meta-analysis to gain a better understanding of the prognostic value of lncRNAs in patients with varian carcinoma. We systematically searched PubMed, EMBASE, and Web of Science. A total of 13 eligible studies, including 10 on clinicopathological features, 13 on prognosis were identified. Pooled hazard ratios (HRs) or odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. Our results revealed that the increased expressions of 8 lncRNAs were associated with poor prognosis and the decreased expressions of 5 lncRNAs were related to poor prognosis in ovarian carcinoma. High HOTAIR expression was associated with shorter overall survival in ovarian cancer (pooled HR: 2.05, 95% CI: 1.51-2.77, P < 0.001). In conclusion, our meta-analysis suggested that LncRNAs could function as potential prognostic markers for ovarian cancer patients and high expression HOTAIR was associated with shorter overall survival in ovarian cancer.

Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons.

Shank proteins assemble glutamate receptors with their intracellular signaling apparatus and cytoskeleton at the postsynaptic density. Whether Shank plays a role in spinogenesis and synaptogenesis remained unclear. Here, we report that knock-down of Shank3/prolinerich synapse-associated protein-2 by RNA interference reduces spine density in hippocampal neurons. Moreover, transgene expression of Shank 3 is sufficient to induce functional dendritic spines in aspiny cerebellar neurons. Transfected Shank protein recruits functional glutamate receptors, increases the number and size of synaptic contacts, and increases amplitude, frequency, and the AMPA component of miniature EPSCs, similar to what is observed during synapse developmental maturation. Mutation/deletion approaches indicate that these effects require interactions of Shank3 with the glutamate receptor complex. Consistent with this observation, chronic treatment with glutamate receptor antagonists alters maturation of the Shank3-induced spines. These results strongly suggest that Shank proteins and the associated glutamate receptors participate in a concerted manner to form spines and functional synapses.

The Significance of Long Noncoding RNA H19 in Predicting Progression and Metastasis of Cancers: A Meta-Analysis.

Recently, numerous studies indicate that H19 plays a key role in tumorigenesis, but the results have been disputed, especially in the aspects of tumor progression and metastasis. Therefore, we performed this meta-analysis to systematically summarize the relationship between H19 and cancers. We searched PubMed, the Cochrane Library, CNKI, and Chinese Wan Fang to identify eligible studies. Odds ratios and 95% confidence intervals were calculated to assess the effect size. A total of 13 studies were enrolled in this meta-analysis, which was performed by Revman5.3 and Stata11.0 software. Our meta-analysis showed that the expression of H19 was associated with distant metastasis in nongastrointestinal tumors (OR = 3.85, 95% CI = 1.31-11.36, P = 0.01) and, in gastrointestinal tumors (OR = 0.34, 95% CI = 0.15-0.78, P = 0.01), lymph node metastasis (OR = 2.04, 95% CI = 1.19-3.48, P = 0.009). Moreover, in gastric cancer, H19 expression was significantly related to histological grade (OR = 0.50, 95% CI = 0.29-0.86, P = 0.01), TNM stage (OR = 0.19, 95% CI = 0.11-0.33, P < 0.01), and tumor invasion depth (OR = 0.11, 95% CI = 0.04-0.27, P < 0.01). Therefore, H19 could serve as a potential marker for progression and metastasis evaluation of cancers.