The Roles of Small Extracellular Vesicles and Small Extracellular Vesicles-derived Non-coding RNA in Non-alcoholic Fatty Liver Disease / 生物化学与生物物理进展

Extracellular vesicles (EVs) are a kind of exsomes secreted by cells, which all cells release them as part of their normal physiology and during acquired abnormalities. EVs can be broadly divided into two categories by their sizes, small EVs (sEVs) and medium/large EVs (m/l EVs). As a kind of extracellular vesicle, sEVs are mostly discoid vesicles with diameters ranging from 40 nm to 200 nm. The medium/large EVs are elliptical with a diameter more than 200 nm. sEVs play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of liver diseases. In this review, we discussed the current understanding of the role of sEVs, particularly sEV derived non-coding RNA in non-alcoholic fatty liver disease (NAFLD) and their potential as diagnostic and therapeutic targets. sEVs are small membrane-bound particles secreted by cells, which fuse with plasma membrane and release to extracellular matrix. Depending on the cell of origin, sEVs could contain many cell constituents, including various DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins, biomolecules. In addition, many RNA and DNA molecules contained by sEVs, such as mRNA, microRNA (miRNA), long noncoding RNA (lncRNA) and mitochondrial DNA (mtDNA), can be transferred to recipient cells to effectively promote their biological response, physiological and pathological functions. Such sEVs-mediated responses can be disease promoting or restraining. The intrinsic properties of sEVs in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases. Recent studies reviewed here also indicate a functional, targeted, mechanism-driven accumulation of specific cellular components in sEVs, suggesting that they have a role in regulating intercellular communication. Many studies have also shown the involvement of sEVs’ noncoding RNAs (ncRNAs) in controlling cell activities and their crucial functions in regulating lipid metabolism. sEVs ncRNAs, including miRNAs, lncRNAs, and circular RNAs (circRNAs) regulate physiological functions and maintain lipid metabolism homeostasis. miRNA are small non-coding RNA molecules that regulate posttranscriptional gene expression by repressing messenger RNA-targets. These circulating miRNAs are easily accessible, disease-specific and sensitive to small changes, which makes them ideal biomarkers for diagnostic, prognostic, predictive or monitoring purposes. Specific miRNA signatures can be reflective of disease status and development or indicators of poor treatment response in liver diseases. And lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. Then circRNAs contributed to NAFLD progression by acting as miRNA sponges, functional protein sponges, or novel templates for protein translation. Finally, sEVs could be engineered to deliver diverse therapeutic payloads, including short interfering RNAs, antisense oligonucleotides and so on, with an ability to direct their delivery to a desired target. The potential of targeting sEVs with lncRNAs and miRNAs not only could be potential diagnostic biomarkers for NAFLD, but also have potential therapeutic effects on NAFLD, which might provide new ideas for the NAFLD treatment. In conclusion, this review provides an overview of the current understanding of the roles of sEVs ncRNAs in NAFLD, so we suggest that further research into sEVs could lead to new diagnostic tools and therapeutic strategies for NAFLD.

Traditional Chinese Medicine Treatment, Gua Sha, can Induce Subtle Molecular Changes in Gene Expression / 生物医学与环境科学（英文）

OBJECTIVE@#Here, we explored molecular changes that could potentially mediate healing effects of Gua Sha - a method employed by the Chinese traditional medicine with proven track records of safe and efficient applications dating back to ancient times as well as support from randomized controlled trials performed by modern medical studies - yet remaining almost entirely unexplored by the modern-day high-throughput methods of the -omics sciences.@*METHODS@#We investigated transcriptome changes occurring shortly after Gua Sha treatment in the whole blood of healthy volunteers using bulk RNA-seq analysis. We applied various analytical tools to identify genes with consistent expression changes in multiple individuals in response to Gua Sha and their networks.@*RESULTS@#We found that while the changes were very subtle and individual-specific, we could identify consistent upregulation of three histone genes. Further analysis of the potential regulatory networks of these histone genes revealed the enrichment of functions involved in the immune response and inflammation.@*CONCLUSION@#The significance of these results in the context of potential effects of Gua Sha and the next steps in exploring the molecular mechanisms of action of this technique are discussed.

Construction of genomic instability⁃associated LncRNA models to predict prognosis and cisplatin sensitivity in colon cancer patients / 安徽医科大学学报

Objective @#To explore whether the long⁃chain noncoding RNA associated with genomic instability in colon cancer can predict clinical prognosis and therapeutic.@*Methods @#The R package " limma" was used for differential analysis , and the prognostic risk model was constructed by univariate Cox analysis and multivariate Cox proportional risk regression analysis. The difference in prognosis was evaluated by Kaplan⁃Meier method , and the difference was significant by log⁃rank test. The efficiency of the prognostic model was evaluated using a time⁃dependent area under the subject operating characteristic curve (AUC) . The R package“ pRRophetic ”was used to predict the sensitivity of patients to anticancer drugs. R software package rms was used to build a line graph , and the consistency index of the line graph was calculated. Real⁃time quantitative PCR was used to detect the difference in the expression levels of prognostic protective factors. @*Results @#A total of 22 LncRNAs associated with genomic instabili⁃y in patients with prognosis were obtained , 2 were protective factors for prognosis in patients with colon cancer, and 20 were risk factors for prognosis. A prognosis model composed of LncRNAs associated with genomic instability was constructed , and patients with high risk scores had lower AUCs and shorter median survival. The five⁃year survival AUC predicted by the model was 0. 823 in the training set , 0. 722 in the validation set , and 0. 759 in the overall TCGA colon cancer patient population. Patients with low risk scores had lower half inhibitory concentration (IC50 ) of cisplatin and higher sensitivity (P < 0. 000 1) . The expression of prognostic protective factors in colon cancer tissues was significantly lower than that in adjacent colon cancer tissues. @*Conclusion @#A prognostic risk model composed of 8 LncRNAs associated with genomic instability was constructed and verified. In addition , the model can also predict cisplatin drug sensitivity. A histogram was constructed combining the tumor stage and the prognosis model. The predictive ability of this graph for five⁃year survival of colon cancer patients is better than that of traditional histopathological features and prognostic models constructed by predecessors.

The possibility of early diagnosis of colorectal cancer through expression of Lncrna UCA1, Lncrna LINC00970, and Wnt genes; an in-vitro study

Colorectal cancer is the 4thcause of cancer death; with considering the growth process of this cancer and the necessity of early diagnosis, the purpose of the research is to state the LncRNA 00970, LncRNA UCAI,and the Wntgene before and after the treatment by 5-Azacytidine epigenetic medicine, to reach the biomarker in the very first steps of colorectal cancer. In this experiment, the human colon cancer cell line (HT29) treated with different concentrations of 5-aza-2'-deoxycytidine (5-aza-dC) was utilized to induce DNA demethylation; Quantitative PCR (qPCR) was used to measure LncRNA UCA1and LncRNA LINC00970 and Wntexpression. There was a significant relationship between the expression of LncRNA 00970, LncRNA UCAI,and the Wntgene and its effects on colorectal (p < 0.05). The Wntgene was treated by 1 and 10 of 5-Azacytidine epigenetic medicine, which then experienced decreases. In LncRNA UCAI and LncRNA00970 in dose 1 micromolar of 5-Azacytidine had decrement and increment of expressionrespectively that explains their efficiency but in treatment by dose 10 mM of this medicine, no significant LncRNA expression difference was detected, 5-azacitidine has a direct impact on its target genes and LncRNAs.Therefore, it can be used in the early diagnosis of colorectal cancer.

Research progress of lncRNA regulating miRNA in osteoarthritis / 中国综合临床

Non-coding RNAs (ncRNAs), which are thought to regulate articular cartilage through endochondral osteogenesis, consist of mRNA-interfering complementary RNA (miRNA) and long non-coding RNAs (lncRNA). More and more experimental evidence reveals the role of ncRNAs in chondrocyte differentiation and the pathogenesis of several skeletal diseases, including osteoarthritis. In the past few years, increasingly sophisticated DNA sequencing methods and a large number of sepigenetic modifications have greatly contributed to our understanding of the pathophysiological mechanisms of osteoarthritis. Recent studies have revealed that RNA interacts with RNA-binding proteins, regulates gene transcription and protein translation, and is involved in various pathological processes in OA, promising to be a therapeutic target for osteoarthritis.

Research progress on the regulatory mechanism of non-coding RNA in arsenic toxicity / 中华劳动卫生职业病杂志

Arsenic is a non-metallic element, and the International Agency for Research on Cancer has identified arsenic and its compounds as carcinogens. Arsenic and its compounds can be absorbed through the respiratory tract, skin and digestive tract, distributed in the liver, kidney, lung and skin, and cause damage. Non-coding RNAs are closely related to arsenic-induced nervous system disorders, cell necrosis, reproductive toxicity, and carcinogenesis. In recent years, the network regulation of microRNAs (miRNAs) , long non-coding RNAs (lncRNAs) , and circular RNAs (circRNAs) among non-coding RNAs in various diseases induced by arsenic has become a new research field. This paper summarizes the existing scientific research results, and expounds the mechanism of miRNAs, lncRNAs and circRNAs in arsenic toxicity, and provides basic data and theoretical basis for the prevention and treatment of arsenic poisoning.

m7G-lncRNAs are potential biomarkers for prognosis and tumor microenvironment in patients with colon cancer / 南方医科大学学报

OBJECTIVE@#To assess the value of m7G-lncRNAs in predicting the prognosis and microenvironment of colorectal cancer (CRC).@*METHODS@#We screened m7G-lncRNAs from TCGA to construct an m7G-lncRNAs risk model using multivariate Cox analysis, which was validated using ROC and C-index curves. Calibration and nomogram were used to predict the prognosis of CRC patients. Point-bar charts and K-M survival curves were used to assess the correlation of risk scores with the patients' clinical staging and prognosis. CIBERSORT and ESTIMATE were used to explore the association between the tumor microenvironment and immune cell infiltration in patients in high and low risk groups and the correlation of risk scores with microsatellite instability, stem cell index and immune checkpoint expression. A protein-protein interaction network was constructed, and the key targets regulated by m7G-lncRNAs were identified and validated in paired samples of CRC and adjacent tissues by immunoblotting.@*RESULTS@#We identified a total of 1722 m7G-lncRNAs from TCGA database, from which 12 lncRNAs were screened to construct the risk model. The AUCs of the risk model for predicting survival outcomes at 1, 3 and 5 years were 0.727, 0.747 and 0.794, respectively. The AUC of the nomogram for predicting prognosis was 0.794, and the predicted results were consistent with actual survival outcomes of the patients. The patients in the high-risk group showed more advanced tumor stages and a greater likelihood of high microsatellite instability than those in the low-risk group (P < 0.05). The tumor stemness index was negatively correlated with the risk score (r=-0.19; P=7.3e-05). Patients in the high-risk group had higher stromal cell scores (P=0.0028) and higher total scores (P=0.007) with lowered expressions of activated mast cells (r=-0.11; P=0.045) and resting CD4+ T cells (r=-0.14; P=0.01) and increased expressions of most immune checkpoints (P < 0.05). ATXN2 (P= 0.006) and G3BP1 (P=0.007) were identified as the key targets regulated by m7G-lncRNAs, and their expressions were both higher in CRC than in adjacent tissues.@*CONCLUSION@#The risk model based on 12 m7G-lncRNAs has important prognostic value for CRC and can reflect the microenvironment and the efficacy of immunotherapy in the patients.

The expression patterns of MALAT-1, NEAT-1, THRIL, and miR-155-5p in the acute to the post-acute phase of COVID-19 disease

ABSTRACT Introduction: One of the hallmarks of COVID-19 is overwhelming inflammation, which plays a very important role in the pathogenesis of COVID-19. Thus, identification of inflammatory factors that interact with the SARS-CoV-2 can be very important to control and diagnose the severity of COVID-19. The aim of this study was to investigate the expression patterns of inflammation-related non-coding RNAs (ncRNAs) including MALAT-1, NEAT-1, THRIL, and miR-155-5p from the acute phase to the recovery phase of COVID-19. Methods: Total RNA was extracted from Peripheral Blood Mononuclear Cell (PBMC) samples of 20 patients with acute COVID-19 infection and 20 healthy individuals and the expression levels of MALAT-1, NEAT-1, THRIL, and miR-155-5p were evaluated by real-time PCR assay. Besides, in order to monitor the expression pattern of selected ncRNAs from the acute phase to the recovery phase of COVID-19 disease, the levels of ncRNAs were re-measured 6-7 weeks after the acute phase. Result: The mean expression levels of MALAT-1, THRIL, and miR-155-5p were significantly increased in the acute phase of COVID-19 compared with a healthy control group. In addition, the expression levels of MALAT-1 and THRIL in the post-acute phase of COVID-19 were significantly lower than in the acute phase of COVID-19. According to the ROC curve analysis, these ncRNAs could be considered useful biomarkers for COVID-19 diagnosis and for discriminating between acute and post-acute phase of COVID-19. Discussion: Inflammation-related ncRNAs (MALAT-1, THRIL, and miR-150-5p) can act as hopeful biomarkers for the monitoring and diagnosis of COVID-19 disease.

Relationship between spinal lncRNA and kindlin-1/Wnt3a signaling pathway in a rat model of neuropathic pain / 中华麻醉学杂志

Objective:To investigate the relationship between spinal long chain noncoding RNA (lncRNA) and kindlin-1/Wnt3a signaling pathway in a rat model of neuropathic pain (NP).Methods:The experiment was performed in two parts.Experiment Ⅰ Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were selected.Rats were sacrificed, the dorsal horn of spinal cord was removed, and the primary astrocytes were extracted and cultured.Lipopolysaccharide 1 μg/ml was added to induce the activation of astrocytes for 24 h. The lncRNA binding to kindlin-1 was identified using PCR immunoprecipitation method.The localization of lncRNA FOXF1-AS1 in astrocytes was observed by fluorescence in situ hybridization, and the binding between lncRNA FOXF1-AS1 and kindlin-1 was detected by biotin-labeled magnetic bead method.Experiment Ⅱ Thirty clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 250-280 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation control group (group C), NP group, lncRNA FOXF1-AS1 overexpression group (group F), lncRNA FOXF1-AS1 overexpression plus kindlin-1 shRNA group (group FK) and lncRNA FOXF1-AS1 overexpression + Wnt inhibitor group (group FW). NP was induced by chronic constrictive injury in anesthetized animals.In group F, lncRNA FOXF1-AS1 overexpression lentivirus 10 μl was intrathecally injected at 28 days before operation, and vector virus 10 μl was intrathecally injected in the other groups.In FK group, kindlin-1 interfering shRNA interference adenovirus 10 μl, and vector virus 10 μl was intrathecally injected in the other groups.In group FW, Wnt inhibitor IWP-2 10 μl was intrathecally injected at 1-3 days after operation, artificial cerebrospinal fluid 10 μl was intrathecally injected at the same time point in the other groups.Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1 day before operation, at 4 days and 7 days after operation.The animals were sacrificed at the end of measurement of pain threshold at 7 days after operation, and the spinal cord tissues were taken for determination of the expression of kindlin-1, Wnt3a and glial fibrillary acidic protein (GFAP) (by Western blot) and the contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β (IL-1β) (using enzyme-linked immunosorbent assay). Results:ExperimentⅠ lncRNA FOXF1-AS1, which was expressed in the cytoplasm of astrocytes, combined with kindlin-1.Experiment Ⅱ Compared with C group, MWT was significantly decreased, TWL was shortened at 4 and 7 days after operation, the expression of kindlin-1, Wnt3a and GFAP in spinal cord was up-regulated, and the contents of TNF-α and IL-1β were increased in group NP ( P<0.05). Compared with NP group, MWT was significantly decreased, TWL was shortened at 4 and 7 days after operation, the expression of kindlin-1, Wnt3a and GFAP in spinal cord was up-regulated, and the contents of TNF-α and IL-1β were increased in F group, MWT was increased, TWL was prolonged at 4 and 7 days after operation, and the contents of TNF-α and IL-1β were decreased in group FK and group FW, the expression of kindlin-1, Wnt3a and GFAP was down-regulated in group FK, and the expression of kindlin-1 was up-regulated, and expression of Wnt3a and GFAP was down-regulated in group FW ( P<0.05). Compared with group F, MWT was significantly increased, TWL was prolonged at 4 and 7 days after operation, and the contents of TNF-α and IL-1β were decreased in group FK and group FW, the expression of spinal kindlin-1, Wnt3a and GFAP was down-regulated in group FK, and expression of Wnt3a and GFAP was down-regulated in group FW ( P<0.05). Conclusion:lncRNA FOXF1-AS1 can up-regulate kindlin-1 expression, activate Wnt3a signaling pathway, promote astrocyte activation, and then regulate inflammatory responses and is involved in the process of neuropathic pain in rats.

LncRNA-599554 sponges miR-15a-5p to contribute inductive ability of dermal papilla cells through positive regulation of the expression of Wnt3a in cashmere goat

BACKGROUND: Long non-coding RNAs (lncRNAs), as post-transcriptional regulators, were thought to function in the inductive property of dermal papilla cells (DPCs) in cashmere goat. Previously, lncRNA-599554 was identified in secondary hair follicle (SHF) of cashmere goat, but its functional significance is unknown. RESULTS: In the present investigation, we verified that lncRNA-599554 had significantly higher expression at the anagen dermal papilla of cashmere goat SHF than that at telogen. Based on overexpression and knockdown techniques, we found that lncRNA-599554 contributes the inductive property of DPCs of cashmere goat, which was assessed by detecting the changes in the expression of several typical indictor genes in DPCs including ET-1, SCF, Versican, ALP, Lef1 and Ptc-1. Based on RNA pull-down assay, we verified that lncRNA-599554 directly interacted with chi-miR-15a-5p. Also, we showed that lncRNA-599554 positively regulated the Wnt3a expression in DPCs but which did not appear to involve its modulating of promoter methylation. Based on the use of Dual-luciferase reporter assays, our data indicated that lncRNA-599554 regulated the Wnt3a expression through chi-miR-15a-5p-mediated post-transcriptional level. CONCLUSIONS: We showed that lncRNA-599554 contributes the inductive property of DPCs in cashmere goat which might be achieved through sponging chi-miR-15b-5p to promote the Wnt3a expression. The results from the present investigation provided a novel insight into the functional mechanism of lncRNA-599554 in the SHF regeneration of cashmere goat along with the formation and growth of cashmere fiber.

Effect of electroacupuncture pretreatment on differential expression profiles of myocardial long non-coding RNA and mRNA in mice with myocardial ischemia-reperfusion injury / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Neiguan" (PC6) on expression profiles of myocardial long non-coding RNAs (LncRNAs) and mRNAs in myocardial ischemia-reperfusion injury (MIRI) mice, so as to explore its mechanisms underlying prevention of MIRI via regulating LncRNA expression. METHODS: C57BL/6 mice were randomly divided into sham, model, and EA groups (n=4 in each group). The MIRI model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 30 min, followed by reperfusion for 24 h. In the sham group, the ADB was only threaded beneath the artery without ligation. EA was applied to bilateral PC6 for 30 min prior to ischemia induction. Surgery was performed within 30 min at the end of EA stimulation. The expression profiles of differentially expressed LncRNAs and mRNAs in the left ventricular myocardium were analyzed by using LncRNA microarray. RESULTS: There was a significant diffe-rence in the expression pattern of LncRNAs and mRNAs among the sham, model and EA groups. A total of 1 693 LncRNAs and 2 858 mRNAs between the model and sham groups, and 3 859 LncRNAs and 1 343 mRNAs between the EA and model groups were identified to be differentially expressed candidates. According to Venn intersection analysis, LncRNAs with opposite regulative orientations in the model and EA groups were screened and defined as EA-related LncRNAs. LncRNA-mRNA co-expression analysis and Gene Ontology enrichment analysis of the EA-related LncRNAs predicted their roles to regulating post-traumatic stress and repairing of myocardial cells. Meanwhile, the proteins' function encoded by EA-related mRNAs mainly involved post-traumatic stress and inflammatory regulation. CONCLUSION: EA pretreatment at PC6 acupoint can produce extensive regulation on myocardial LncRNAs and mRNAs in MIRI mice, suggesting an involvement of LncRNAs in EA pretreatment induced improvement of MIRI. These results may provide direction and molecular basis for subsequent in-depth studies to reveal the underlying mechanisms of EA pretreatment for MIRI.

ADAMTS9-AS1-SEMA3G affects the infiltration of immune cells in pancreatic cancer / 医学研究生学报

ObjectiveThe mechanism that affects the infiltration of immune cells in pancreatic cancer has not yet been clarified. This study aims to investigate the lncRNA mRNA regulatory pathways that affect immune infiltration in pancreatic cancer.MethodsTCGA and GEO gene expression data were used to screen common differential lncRNAs. We perform survival analysis, target gene prediction, GO, KEGG enrichment analysis, immune infiltration analysis, gene set enrichment analysis (GSEA) on the selected differential lncRNAs to identify the relevant pathways of immune infiltration.ResultsThe pancreatic cancer patients with high expression of ADAMTS9 AS1 have a higher survival rate when compared to patients with low expression (P=0.010). The combined analysis of TCGA and GSE86436 revealed the difference and survival-related ADAMTS9 AS1. The functional prediction of ADAMTS9 AS1 was related to immunity. Using the TIMER database, the lncRNA affected the infiltration of immune cells in pancreatic cancer tissues. The clinical analysis was demonstrated that the ADAMTS9 AS1 was related to pathological grade. The target gene SEMA3G was screened by co-expression analysis using the IMMPORT database and TIMER database. Lastly, GSEA analysis of ADAMTS9-AS1 showed that the lncRNA was also related to tumor metabolism.ConclusionThese results indicate that ADAMTS9-AS1-SEMA3G is associated with the prognosis and immune invasion level of pancreatic cancer, which can provide a theoretical basis for subsequent genetic verification experiments and immune research.

Long non-coding RNA MIR210HG promotes growth and invasion of glioblastoma / 第二军医大学学报

Objective To screen the differentially expressed long non-coding RNAs (lncRNAs) in glioblastoma, and to explore its role in the growth and invasion of glioblastoma. Methods Eight matched glioblastoma tumor tissues and peritumoral tissues were selected for high-throughput hybridization experiments, and the lncRNA with largest expression difference was screened. Human glioblastoma cell models with overexpression and interference expression of the lncRNA were established. Cell counting kit-8 (CCK-8) was used to detect the cell proliferation ability, flow cytometry was used to detect the apoptosis level, and Transwell assay was used to detect the cell invasion and migration abilities. Results The lncRNA MIR210HG, which was highly expressed in glioblastoma tissues, was screened out, and the glioblastoma cell models with overexpression and interference expression of lncRNA MIR210HG were successfully constructed. In vitro experiments showed that after overexpression of lncRNA MIR210HG, the apoptosis level of the glioblastoma cells was decreased, and the proliferation, invasion and migration abilities were increased, and after interference expression of lncRNA MIR210HG, the apoptosis level of the glioblastoma cells was increased, and the proliferation, invasion and migration abilities were decreased, with significant differences compared with control group (all P<0.05). Conclusion LncRNA MIR210HG can inhibit the apoptosis of glioblastoma cells, and promote cell proliferation, invasion and migration; and it may serve as a new target of glioblastoma therapy.

The role of the membrane of the maxillary sinus in space osteogenesis under the sinus floor after elevation of the sinus floor / 口腔疾病防治

@#With the continuous development of maxillary sinus floor elevation technology, the osteogenesis mechanism of maxillary sinus floor elevation has always been a concern of scholars. The membrane of the maxillary sinus is an indispensable physiological structure in the process of space osteogenesis under the sinus floor after elevation of the sinus floor. In recent years, the role of the maxillary sinus floor mucosa in sinus floor space osteogenesis has been a research hotspot. Recent studies have found that the maxillary sinus floor membrane plays a role as a natural biological barrier membrane in the process of sinus floor space osteogenesis after maxillary sinus floor elevation; in addition, it has the ability to undergo osteogenesis. It has also been found that maxillary sinus membrane stem cells (MSMSCs) derived from the maxillary sinus floor membrane have characteristics of mesenchymal stem cells, which can differentiate into osteoblasts and participate in sinus floor space osteogenesis after maxillary sinus floor elevation. New studies have also found that small RNAs such as microRNAs, long noncoding RNAs and circular RNAs can regulate the osteogenic differentiation of MSMSCs, which may be important biological targets for promoting osteogenesis in the sinus floor space. In this paper, the relationship between the maxillary sinus floor mucosa and bone formation after maxillary sinus floor elevation, the barrier and osteogenic function of the maxillary sinus floor mucosa, the sources of osteoblasts involved in osteogenesis of the sinus floor space, and the molecular regulatory mechanisms of stem cells derived from maxillary sinus mucosa will be elucidated step by step.

Long non-coding RNAs: Fine-tuning the developmental responses in plants

Plant developmental biology is associated with various gene regulatory pathways involved in different phases of their lifecycle. In course of development, growth and differentiation of different organs in plants are regulated by specific sets ofgene expression. With the advances in genomic and bioinformatic techniques, particularly high-throughput sequencingtechnology, many transcriptional units with no protein-coding potential have been discovered. Previously thought to be thedark matters of genome, long non-coding RNAs (lncRNAs) are gradually gaining importance as crucial players in generegulation during different developmental phases. Some lncRNAs, showing complementarity to microRNAs (miRNAs), areused as endogenous target mimics of specific miRNA family. A number of lncRNAs can also act as natural antisensetranscripts to attenuate the expression of coding genes. Although lncRNA-mediated regulations have extensively beenstudied in animals, plant lncRNA research is still in its initial phase. The present review highlights the regulatory mechanism and different physiological aspects of lncRNAs in plant development. In plants, lncRNAs are found to be associatedwith a number of plant developmental functions such as lateral root development, vernalization, photomorphogenesis,pollen development, fiber development and nodulation. Understanding these potent roles of lncRNAs in plant developmentcan further provide novel tools for crop improvement programs in future.

Los ARNs no codificantes largos y su vinculación con las patologías testiculares / Long non-coding RNAs and their involvement in testicular pathologies / RNAs longos não-codificantes e sua ligação com patologias testiculares

Si bien la porción del genoma destinada a la síntesis de proteínas es muy pequeña, actualmente se sabe que casi todo el genoma se expresa bajo forma de ARNs no codificantes. Entre dichos ARNs se encuentran los ARNs no codificantes largos (lncRNAs). Aunque los lncRNAs han sido muy poco estudiados, recientemente han comenzado a centrar la atención de los investigadores, al descubrirse que los mismos pueden desempeñar diversas funciones en la regulación de la expresión génica. Además, su vinculación con patologías ha comenzado a ser puesta de manifiesto. Curiosamente, la cantidad de lncRNAs presentes en el testículo es abrumadoramente mayor que en cualquier otro órgano o tejido estudiado. Los perfiles de expresión de estos lncRNAs varían significativamente a lo largo de la espermatogénesis, y algunas evidencias sugieren que al menos algunos de ellos podrían participar en el proceso de formación de células germinales masculinas. No obstante, el conocimiento sobre el tema es aún muy escaso. En este trabajo revisamos la información disponible sobre la expresión de lncRNAs en el testículo y sus posibles funciones. Asimismo, analizamos algunos ejemplos que ilustran la participación de lncRNAs en el desarrollo de patologías como la infertilidad y el cáncer testicular.

Although the portion of the genome devoted to protein synthesis is very small, it is now known that almost the entire genome is expressed as non-coding RNAs. Among them, there are long noncoding RNAs (lncRNAs). Despite that lncRNAs have been very poorly studied, they have recently started to focus the attention of researchers, as it has been found out that lncRNAs can perform diverse functions in the regulation of gene expression. Besides, their involvement in pathologies is being revealed. Intriguingly, the amount of lncRNAs in the testis is overwhelmingly higher than in any other analyzed organ or tissue. LncRNA expression profiles significantly vary along spermatogenesis, and some evidence suggests that at least some of them could participate in the formation of male germ cells. However, knowledge on the subject is still very scarce. In this work we review the available information on the expression of lncRNAs in testis and their possible roles. We also analyze some examples that illustrate the participation of lncRNAs in the development of pathologies such as infertility and testicular cancer.

Embora a porção do genoma usada para a síntese proteica seja muito pequena, sabe-se agora que quase todo o genoma é expresso na forma de RNAs não-codificantes. Entre esses RNAs estão os longos RNAs não codificantes (lncRNAs). Embora os lncRNAs tenham sido pouco estudados, eles recentemente começaram a focar a atenção dos pesquisadores, ao descobrirem que podem desempenhar diversas funções na regulação da expressão gênica. Além disso, sua ligação com as patologias começou a ser revelada. Curiosamente, a quantidade de lncRNAs presentes nos testículos é esmagadoramente maior do que em qualquer outro órgão ou tecido estudado. Os perfis de expressão destes lncRNAs variam significativamente ao longo da espermatogênese, e algumas evidências sugerem que pelo menos alguns deles poderiam participar no processo de formação de células germinativas masculinas. No entanto, o conhecimento sobre o assunto ainda é muito escasso. Neste trabalho, revisamos as informações disponíveis sobre a expressão de lncRNAs no testículo e suas possíveis funções. Também analisamos alguns exemplos que ilustram a participação dos lncRNAs no desenvolvimento de patologias como infertilidade e câncer testicular.

Emerging roles of long non-coding RNAs in cancer

Cancer is a physiological condition that has both the endogenous and exogenous influences on its progression. It originatesfrom unusual cell growth, where the cells undergo massive genetic alterations, bypass the signaling machinery andcompromise its genetic cohesion. Literature has well narrated the DNA damage studies including driver mutations thatinterfere with the treatment strategies. However, with evolving medical excellence, recent day studies are trying to unveilthe contribution of RNAs in the progression of tumor malignancies. A number of non-coding RNAs have been identified asan active component in cancer genomics. This article aims to review the role of long non-coding RNAs in the spectra ofcancers and its prognostic value as the biomarkers in molecular targeting with clinical utility and therapeutic beneficence.

Mechanisms of Huangqi Decoction Granules () on Hepatitis B Cirrhosis Patients Based on RNA-Sequencing / 中国结合医学杂志

OBJECTIVE@#To explore the action mechanisms of Huangqi Decoction Granules (, HQDG) on hepatitis B cirrhosis.@*METHODS@#A total of 85 patients with hepatitis B cirrhosis were randomly divided into HQDG group (42 cases) and control group (43 cases) by a random number table and were treated with HQDG or placebo for 48 weeks (6 g per times and orally for 3 times a day), respectively. After RNA-sequencing of serum samples extracted from the patients, the differentially expressed genes (DEGs) in HQDG and control groups before and after treatment were separately screened. The DEGs were then performed pathway enrichment analysis and proteinprotein interaction (PPI) network analysis. The expression levels of key genes were detected by quantitative realtime polymerase chain reaction (qRT-PCR).@*RESULTS@#After the investigation, 4 and 3 cases were respectively excluded from HQD and control groups because of the incomplete data. Additionally, 3 and 5 cases were lost to follow up in HQD and control groups respectively. Finally, a total of 70 cases with good compliance were included for further DEGs analysis. A total of 1,070 DEGs (including 455 up-regulated genes and 615 down-regulated genes) in HQDG group and 227 DEGs (including 164 up-regulated genes and 63 down-regulated genes) in the control group were identified after treatment. Compared with the control group, 1,043 DEGs were specific in HQDG group. Besides, 1 up-regulated transcription factor (TF, such as GLI family zinc finger 1, GLI1) and 25 down-regulated TFs (such as drosophila mothers against decapentaplegic proteinfamily member 2, SMAD2) were identified. Pathway enrichment analysis showed that down-regulated Ras homolog gene family member A (RHOA) was enriched in pathogenic Escherichia coli infection. In the PPI network, up-regulated epidermal growth factor receptor (EGFR), and down-regulated cell division cycle 42 (CDC42) as well as v-akt murine thymoma viral oncogene homolog 1 (AKT1) had higher degrees. Moreover, long non-coding RNAs (lncRNA) growth arrest-specific 5 (GAS5) was involved in the lncRNA-target regulatory network. Furthermore, qRT-PCR revealed that expression levels of CDC42 and GLI1 had significant differences in HQDG group before and after treatment (P<0.05).@*CONCLUSIONS@#CDC42 and GLI1 may be the targets of HQDG in patients with hepatitis B cirrhosis. Additionally, SMAD2, EGFR, AKT1, RHOA and GAS5 might be associated with the curative effect of HQDG on hepatitis B cirrhosis patients.

Long non-coding RNAs show different expression profiles and display competing endogenous RNA potential in placenta accreta spectrum disorders / 南方医科大学学报

OBJECTIVE@#To investigate the expression profile of long non-coding RNAs (lncRNA) and identify potential lncRNA-related competing endogenous RNAs (ceRNA) in placenta accrete spectrum disorders (PAS).@*METHODS@#Five tissue specimens of placental implantation and 5 adjacent normal placental tissues were collected from cesarean section deliveries complicated by PAS in our hospital between December, 2017 and June, 2018. Human microarrays were used to identify the lncRNAs that were differentially expressed in PAS, and 5 of the identified lncRNAs were further validated using qRT-PCR. GO and KEGG pathway analyses were performed to indentify the most significant enrichment functions. A ceRNA network was constructed based on ENST00000511361 (RP5-875H18.4), NR_027457 (LINC00221) and NR_126415 (FOXP4-AS1) to pinpoint the potential lncRNAs-related ceRNA.@*RESULTS@#A total of 329 lncRNAs and 179 mRNAs were identified to have differential expression in PAS. The results of qRT-PCR were consistent with the human microarrays results. Transforming growth factor-β (TGF-β) signaling pathway was the most significantly enriched pathway. The constructed ceRNA network suggested that RP5-875H18.4--miRNA-218--SLIT2 had a potential ceRNA regulatory mechanism in PAS.@*CONCLUSIONS@#The differentially expressed lncRNAs are involved in the occurrence and progression of PAS possibly by regulating the TGF-β signaling pathway. The ceRNA network of RP5-875H18.4--miRNA-218--SLIT2 may play a role in the occurrence of PAS.

Long non-coding RNA and cervical cancer / 生物工程学报

Long non-coding RNAs (lncRNAs) are members of RNA that are structurally similar to mRNA. They cannot encode proteins because they do not have a conserved open reading frame. LncRNAs were once regarded as abnormalities or noises or without any biological function after gene transcription. With the further development of research, it has been found that it can participate in normal or abnormal biological processes as an important regulator. LncRNAs are closely related to the development of nervous system function, metabolic disorders and tumors. LncRNAs abnormally expressed in cervical cancer participate in the regulation of various biological processes of cervical cancer by inhibiting or promoting tumors. This article reviews the recent reports on the abnormal regulation, molecular regulation mechanism and potential clinical application of lncRNAs in cervical cancer.