Clinicopathological and prognostic significance of TINCR in caner: A meta-analysis

BackgroundIn a variety of cancers, the expression of TINCR is linked to the development, progression, metastasis, invasion, and prognosis of cancer. Our study is the first study used meta-analysis to explore the relationship between TINCR expression and cancer.MethodsBy looking up PubMed, Web of Science, CNKI database, we obtained 10 articles for analysis. The statistical analysis was all calculated by Stata 15.1 software.ResultsWe found that the expression of TINCR was a risk factor to the size of the tumor (OR = 1.772, 95%CI: 1.246–2.520, P = 0.001). In univariate analysis, patients with high expression of TINCR had poor OS (pooled HR = 1.533, 95%CI: 1.025–2.294, P = 0.038). Similar result was also found in multivariate analysis In subgroup analysis (pooled HR = 1.610, 95%CI: 1.356–1.913, P = 0.000).We also found that over-expression of TINCR had poor OS in breast cancer (pooled HR = 1.582, 95%CI: 1.126–2.223, P = 0.008).ConclusionIn this study, we found that over-expression of TINCR may influence the tumor size and contribute to the poor prognosis of cancer.     

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.     

Comprehensive analysis of tumor immune infiltration associated with endogenous competitive RNA networks in lung adenocarcinoma

Cancer immunotherapy has achieved unprecedented success in the treatment of cancer. However, different patients have different responses to immunotherapy. More and more studies have shown that tumor immune heterogeneity has an important influence on the prognosis of cancer. Therefore, understanding the clinical impact of tumor immune infiltration and the regulatory mechanism of RNA molecules is crucial for exploring the pathogenesis of lung adenocarcinoma (LUAD) and the development of immunotherapy protocols.The endogenous competitive RNA hypothesis provides new ideas for studying immune heterogeneity. Therefore, by using the method of immune genomics, this article explores the relationship between immune infiltration and prognosis of patients with lung adenocarcinoma, and found that B-cell immune infiltration highly affects the survival of patients. Through differential analysis, differential mRNAs, lncRNAs and miRNAs were extracted, and 318 differentially expressed mRNAs related to B cell immunity were screened by correlation analysis, and prognosis of patients with COX risk regression model was predicted and analyzed. Through multiple database searches, an immune-related ceRNA regulatory network was constructed, containing 3 key mRNAs, 4 miRNAs, and 50 lncRNAs. Three mRNAs and most miRNAs, lncRNAs, are significantly associated with LUAD prognosis. Bioinformatics analysis of the network showed that LINC00337 may up-regulate the expression of PBK and KIF23 through competitive binding of has-mir-373 and has-mir-519d. The competitive binding of has-mir-373 and has-mir-372 can up-regulate the expression of SLC7A11. The interaction between these RNAs may have an important regulatory role in the immune infiltration in lung adenocarcinoma, thereby affecting the patient's prognosis and immunotherapy efficacy.     

Intratumoral heterogeneity of esophageal squamous cell carcinoma and its clinical significance

Recent studies have shown that intratumoral heterogeneity is prevalent in esophageal squamous cell cancer (ESCC) based on DNA sequencing and chromosome analysis in multiple regions from the same tumor. This study aimed to investigate the expression of ZNF750, EP300, MTOR and KMT2D and their intratumoral heterogeneity (ITH) in patients with ESCC. A total of 106 cases, who underwent esophagectomy from 2008 to 2010, with two foci from each case, were tested by immunohistochemistry(IHC) as well as 12 cases were tested by RNAscope in this study.We found that 58/106 (54.72%), 66/106 (62.26%), 75/106 (70.75%%) of ESCC showed high expression of ZNF750, EP300, MTOR, respectively by IHC, and 8/12 (66.67%), 10/12 (83.33%), 4/12 (33.33%) and 6/12 (50%) showed high expression of ZNF750, EP300, MTOR and KMT2D, respectively by RNAscope. Multivariate analysis showed that MTOR expression was an independent infavorable prognostic factor of overall survival (OS) (HR?=?1.921; P?=?0.000). This study also found that 44/106(4151%), 37/106 (34.91%), 39/106(36.79%) of ESCC showed heterogeneous expression of ZNF750, EP300 and MTOR respectively by IHC, 8/12(66.67%), 8/12(66.67%), 4/12(33.33%), 4/12(33.33%) of ZNF750, EP300, MTOR and KMT2D respectively by RNAscope, IHC and RNAscope could successfully detect a high prevalence of ITH. In conclusion, findings of this study showed that ZNF750, EP300, MTOR and KMT2D heterogeneously expressed in ESCC. High expression of ZNF750 related to a better outcome, while EP300 and MTOR related to a poor prognosis.     

Feasibility of using dried blood spots for HIV viral load testing among HIV-infected individuals in Thailand using QIAGEN QIAsymphony-artus HIV-1 platform

In settings where plasma preparation and sample centralization are not feasible or inconvenient, dried blood spots (DBS) could be used as an alternative specimen to plasma to assess antiretroviral treatment response among HIV-infected individuals. This study was aimed to (1) validate the recent QIAsymphony-artus assay for DBS HIV viral load (VL) and (2) assess the feasibility of measuring HIV VL on DBS using this assay in Thailand. Ethylenediaminetetraacetic acid-blood samples from 99 HIV-infected individuals were used to prepare paired DBS and plasma. Also, DBS samples were shipped to three distant hospitals in the northern region. After short-term storage, DBS were returned by regular post to the AMS laboratory and were re-tested for HIV VL using the same platform. HIV VL results were compared using Pearson's correlation and Bland-Altman analysis. DBS HIV VL fairly correlated to plasma HIV VL (R = 0.62) with a mean difference of 0.02 log₁₀IU/mL (SD = 1.06). A high correlation (R = 0.79) was observed between HIV VL in DBS before and after shipping (mean difference = 0.14 log₁₀IU/mL, SD = 0.74), indicating good stability of HIV RNA in DBS. DBS can be used as an alternative specimen for HIV VL monitoring in Thailand. However, measurement of HIV VL with the QIAGEN QIAsymphony-artus assay should be improved, especially the DBS pre-extraction process.     

长链非编码RNA在糖尿病视网膜病变发展及治疗中的研究进展

DR是世界各地工作年龄段成年人失明的主要原因，其发病机制是多因素的，分子机制尚不完全清楚。长链非编码RNA（lncRNAs）被认为是多细胞功能的关键调节因子，已有证据表明其参与了DR的许多病理生理机制，本文就 lncRNAs在DR中发挥功能的分子机制及调控作用进行综述，为今后DR的防治研究提供一定的策略和方向。     

脑胶质瘤干细胞衍生的外泌体lncRNA HOXA-AS2促进脑胶质瘤的增殖、迁移、侵袭和干细胞特性

背景与目的：外泌体是介导肿瘤微环境中肿瘤细胞与受体细胞间相互作用的重要信使。然而，细胞外泌体长链非编码RNA（long non-coding RNA，lncRNA）在脑胶质瘤干细胞（glioma stem cell，GSC）和脑胶质瘤细胞的细胞间通信中的作用尚不清楚。本研究探究外泌体衍生的lncRNA对脑胶质瘤增殖、迁移、侵袭和干细胞特性的影响。方法：从中国脑胶质瘤基因组图谱（the Chinese Glioma Genome Atlas，CGGA）和癌症基因组图谱（the Cancer Genome Atlas，TCGA）数据库下载包含低级别脑胶质瘤（low-grade glioma，LGG）和高级别脑胶质瘤（high-grade glioma，HGG）lncRNA表达数据的数据集，识别LGG和HGG组织之间的差异表达lncRNA（differentially expressed lncRNA，DelncRNA），并分析HOXA-AS2水平与胶质瘤患者总生存期（overall survival，OS）之间的关系。从人胶质瘤细胞系SHG44中分离GSC，用流式细胞术检测CD133⁺富集的细胞，再用蛋白质印迹法（Western blot）检测干细胞相关蛋白（CD133、SOX2和OCT4）的表达水平。提取和识别SHG44-GSC衍生的外泌体，并用PKH26细胞膜染料进行荧光标记；再将转染了Cy3标记HOXA-AS2的SHG44-GSC与SHG44细胞进行间接共培养；后用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）检测SHG44-GSC和SHG44-GSC衍生外泌体中HOXA-AS2的水平。使用pLVX-IRES-PURO HOXA-AS2慢病毒质粒和含靶向HOXA-AS2质粒的慢病毒shRNA进行慢病毒转染。采用细胞计数试剂盒-8（cell counting kit-8，CCK-8）和transwell实验检测SHG44-GSC衍生的外泌体HOXA-AS2对SHG44细胞增殖和侵袭能力的影响。结果：HOXA-AS2在胶质瘤中呈现高表达，且与患者较差的OS相关（P<0.01）。SHG44-GSC中CD133⁺细胞比例明显高于SHG44细胞（P<0.000 1），SHG44-GSC中干细胞相关蛋白（CD133、SOX2和OCT4）的表达水平明显高于亲代SHG44细胞（P<0.000 1），并且SHG44-GSC中HOXA-AS2水平显著升高（P<0.000 1）。PKH26标记的外泌体被SHG44细胞吸收，且SHG44细胞中可观察到Cy3标记的HOXA-AS2；HOXA-AS2 OE转染的SHG44-GSC细胞（SHG44-GSC/HOXA-AS2 OE）和SHG44-GSC/HOXA-AS2 OE衍生的外泌体（SHG44-GSC/HOXA-AS2 OE-Exo）中HOXA-AS2水平显著升高（P<0.01），在与SHG44-GSC/HOXA-AS2 OE细胞共培养的SHG44细胞中HOXA-AS2水平显著升高（P<0.01）。SHG44-GSC/HOXA-AS2 OE-Exo可显著促进SHG44细胞增殖、迁移和侵袭。结论：来自SHG44-GSC的外泌体HOXA-AS2能显著促进胶质瘤细胞增殖、迁移、侵袭和干细胞特性，提示HOXA-AS2可能是脑胶质瘤潜在的治疗靶点。     

Binding site comparisons for target-centered drug discovery

Introduction: The success of binding site comparisons in drug discovery is based on the recognized fact that many different proteins have similar binding sites. Indeed, binding site comparisons have found many uses in drug development and have the potential to dramatically cut the cost and shorten the time necessary for the development of new drugs.

Areas covered: The authors review recent methods for comparing protein binding sites and their use in drug repurposing and polypharmacology. They examine emerging fields including the use of binding site comparisons in precision medicine, the prediction of structured water molecules, the search for targets of natural compounds, and their application in the development of protein-based drugs by loop modeling and for comparison of RNA binding sites.

Expert opinion: Binding site comparisons have produced many interesting results in drug development, but relatively little work has been done on protein–protein interaction sites, which are particularly relevant in view of the success of biological drugs. Growth of protein loop modeling for modulating biological drugs is anticipated. The fusion of currently distinct methods for the comparison of RNA and protein binding sites into a single comprehensive approach could allow the search for new selective ribosomal antibiotics and initiate pharmaceutical research into other nucleoproteins.