Roles of Long Noncoding RNAs and Glycolysis in Digestive System Tumors / 中山大学学报(医学科学版)

Long noncoding RNAs （LncRNAs）， a class of noncoding RNAs greater than 200 bases in length， are widely involved in the initiation， progression and glycolytic processes of many tumors， and can act as competitive endogenous RNA sponges to absorb miRNAs. LncRNAs can also inhibit miRNA expression， thereby regulate the glycolysis of tumor cells， affects cell proliferation， invasion and other biological activities. This review explores the roles of LncRNAs and glycolysis in digestive system tumors （DST）， a representative group of malignant tumors. Extending the LncRNA role in the diagnosis， treatment and prognosis of other tumors， we conclude that LncRNAs have the potential to be new candidate genes for tumorigenesis and serve as tumor biomarkers， which provides new insight into morbidity and mortality decrease of DST and other tumors.

The tumor therapeutic potential of long non-coding RNA delivery and targeting

Long non-coding RNAs (lncRNAs) is a type of RNA over 200 nt long without any protein coding ability, which has been investigated relating to crucial biological function in cells. There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment. However, compared to some small non-coding RNA, lncRNA-based drugs are limited in clinical application. Different from other non-coding RNA, like microRNAs, most lncRNAs have a high molecular weight and conserved secondary structure, making the delivery of lncRNAs more complex than the small non-coding RNAs. Considering that lncRNAs constitute the most abundant part of the mammalian genome, it is critical to further explore lncRNA delivery and the subsequent functional studies for potential clinical application. In this review, we will discuss the function and mechanism of lncRNAs in diseases, especially cancer, and different approaches for lncRNA transfection using multiple biomaterials.

Cell cycle related long non-coding RNAs as the critical regulators of breast cancer progression and metastasis

Cell cycle is one of the main cellular mechanisms involved in tumor progression. Almost all of the active molecular pathways in tumor cells directly or indirectly target the cell cycle progression. Therefore, it is necessary to assess the molecular mechanisms involved in cell cycle regulation in tumor cells. Since, early diagnosis has pivotal role in better cancer management and treatment, it is required to introduce the non-invasive diagnostic markers. Long non-coding RNAs (LncRNAs) have higher stability in body fluids in comparison with mRNAs. Therefore, they can be used as efficient non-invasive markers for the early detection of breast cancer (BCa). In the present review we have summarized all of the reported lncRNAs involved in cell cycle regulation in BCa. It has been reported that lncRNAs mainly affect the cell cycle in G1/S transition through the CCND1/CDK4-6 complex. Present review paves the way of introducing the cell cycle related lncRNAs as efficient markers for the early detection of BCa.

Os LncRNAs Estão Envolvidos no Processo de Aterosclerose em Diversos Níveis / LncRNAs are Involved in the Process of Atherosclerosis at Diverse Levels

Resumo A aterosclerose é a causa mais comum de doença cardiovascular em todo o mundo, ela está associada a uma alta incidência de eventos clínicos. O acúmulo de evidências elucidou que os RNAs longos não codificantes (LncRNAs) são uma nova classe de transcritos com papéis críticos nos processos fisiopatológicos da aterosclerose. Nesta revisão, resumimos o progresso recente dos LncRNAs no desenvolvimento da aterosclerose. Descrevemos principalmente os diversos mecanismos regulatórios dos LncRNAs nos níveis transcricionais e pós-transcricionais. Este estudo pode fornecer informações úteis sobre os LncRNAs como alvos terapêuticos ou biomarcadores para o tratamento da aterosclerose.

Abstract Atherosclerosis is the most common cause of cardiovascular disease globally, associated with a high incidence of clinical events. Accumulating evidence has elucidated that long non-coding RNAs (lncRNAs) as a novel class of transcripts with critical roles in the pathophysiological processes of atherosclerosis. In this review, we summarize the recent progress of lncRNAs in the development of atherosclerosis. We mainly describe the diverse regulatory mechanisms of lncRNAs at the transcriptional and post-transcriptional levels. This study may provide helpful insights about lncRNAs as therapeutic targets or biomarkers for atherosclerosis treatment.

Screening and preliminaryfunctional analysis of differentially expressed lncRNAs and mRNAs in vascular endothelial cells treated by tritiated water / 中华放射医学与防护杂志

Objective:To investigate the expression changes of lncRNAs and mRNAs in human umbilical vein endothelial cells(HUVEC) treated by tritiated water.Methods:HUVEC cells were divided into two groups, the control group cultured in DMEM medium, and the tritiated water exposure group cultured in a medium containing tritiated water with a final concentraion of 3.7×10 3 Bq/ml. After culture for 48 h, cells were collected for RNA extract.The differentially expressed lncRNAs and mRNAs were screened by high-through put chip technology and then analyzed. Results:Compared with the control group, 1 717 lncRNAs were significantly up-regulated and 3 994 lncRNAs significantly down-regulated, and 4 562 mRNAs were significantly up-regulated and 1 433 mRNAs down-regulated. Through co-expression analysis of differential mRNAs and lncRNAs, some key genes including SQSTM1, CXCL8, ITPR1, GADD45A, NF-kB1 and VDAC1 were obtained.Conclusions:Tritiated water exposure can induce multiple changes of mRNAs and lncRNAs in vascular endothelial cells, which may lead to toxic effects through signaling pathways including some key genes such as SQSTM1, CXCL8, and ITPR1.

Caracterização funcional do gene codificador de proteína CD14 e do gene não codificador de proteína LINC01133 em linhagens celulares humanas de câncer de mama triplo negativo / Functional characterization of the CD14 protein-coding gene and the non-protein-coding LINC01133 gene in triple negative human breast cancer cell lines

Dentre os subtipos de câncer de mama, o triplo negativo (TNBC) é o que apresenta as maiores taxas de mortalidade, sendo, portanto, considerado um enorme desafio para a clínica. O uso de moléculas como marcadores tumorais vem auxiliando o clínico no diagnóstico, no prognóstico e, até mesmo, no tratamento do TNBC, sendo essenciais na redução de suas altas taxa de mortalidade. No entanto, um pequeno grupo de marcadores tumorais são validados na prática clínica, estimulando à busca por novos alvos, e sua caracterização funcional, como forma de se entender a Biologia desta doença. Assim, o objetivo deste trabalho é caracterizar funcionalmente o gene codificador de proteína CD14 e o gene não codificador de proteína LINC01133 em linhagens celulares humanas de TNBC, no intuito de descobrir o papel destas moléculas na progressão tumoral. Na primeira parte deste trabalho, analisou-se a expressão do CD14 frente à um painel de linhagens celulares que representam os diferentes subtipos dos tumores mamários. O CD14 exibiu elevados níveis de expressão nas linhagens nãotumorigênicas MCF10A e MCF12A e baixos níveis na linhagem triplo negativa Hs578T. A partir destes resultados, o CD14 foi superexpresso na linhagem Hs578T. Ensaios de caracterização funcional mostraram que a superexpressão do CD14 reduziu a capacidade migratória e invasiva das células, efeito que foi hipoteticamente relacionado ao aumento da expressão da E-caderina. No entanto, observou-se aumento no potencial tumorigênico, levando-nos a sugerir seu envolvimento num possível mecanismo utilizado pelas células para compensar a significativa redução do potencial migratório e invasivo. Os resultados obtidos indicam que o nível basal de expressão do CD14 observado na linhagem Hs578T é importante, podendo contribuir para a desenvolvimento primário do tumor, atuando como um oncogene. Na segunda parte deste trabalho, analisou-se a expressão de 10 RNAs longos não codificadores (lncRNAs), frente ao mesmo painel de linhagens descritoanteriormente. Dentre estes, o lncRNA LINC01133 exibiu baixos níveis de expressão nas linhagens não-tumorigênicas MCF10A e MCF12A e elevados níveis na linhagem triplo negativa Hs578T, sendo, então, escolhido como alvo de estudo. A partir destes resultados, decidimos superexpressar, de forma indutível, o LINC01133 na linhagem MCF10A e nocautear este gene, via sistema CRISPR/Cas9, na linhagem Hs578T. Ensaios de caracterização funcional mostraram que a superexpressão do LINC01133 na linhagem MCF10A reduziu a proliferação celular e inibiu o crescimento de colônias dependente de ancoragem, mas, em contrapartida, aumentou o crescimento de colônias independente de ancoragem e a capacidade migratória e invasiva destas células. No entanto, sugerimos que isto não seja suficiente para tornar estas células tumorigênicas e metastáticas. Por outro lado, o nocauteamento do LINC01133 na linhagem triplo negativa Hs578T aumentou de forma considerável todos os parâmetros de malignidade analisados. Baseado nos dados obtidos, sugerimos que o elevado nível de expressão do LINC01133 na linhagem Hs578T é importante na regulação negativa de processos relacionados com a progressão tumoral, atuando com um supressor tumoral. Os dados obtidos em nosso estudo contribuem para o enriquecimento de informações relacionadas à Biologia do TNBC, auxiliando, desta forma, no desenvolvimento de potenciais protocolos clínicos e terapêuticos utilizandos estes biomarcadores

Among the breast cancer subtypes, the triple negative (TNBC) displays the highest mortality rates, being, therefore, considered a major challenge for the clinic. The use of molecules as tumor markers has helped clinicians in the diagnosis, prognosis and even in treatment of TNBC, being essential in reducing its high mortality rate. However, a small group of tumor markers is validated in clinical practice, stimulating the search for new targets, and their functional characterization, as a way to understand the biology of this disease. Thus, the aim of this work is to functionally characterize the CD14 protein-coding gene and the non-protein-coding LINC01133 gene in human TNBC cell lines, in order to probe into the role of these molecules in tumor progression. In the first part of this work, the expression of CD14 was analyzed in a panel of cell lines that represent the different subtypes of breast tumors. High expression levels of CD14 were observed in the non-tumorigenic MCF10A and MCF12A lineages and low levels in the triple negative Hs578T lineage. Based on these results, CD14 was overexpressed in the Hs578T lineage. Functional characterization assays showed that CD14 overexpression reduced the migratory and invasive capacity of cells, an effect that was hypothetically related to increased E-cadherin expression. However, increased in the tumorigenic potential was observed, leading us to suggest its involvement in a possible mechanism used by cells to compensate for the significant reduction in the migratory and invasive potential. The results obtained indicate that CD14 expression basal level observed in the Hs578T lineage may be important to contribute to the primary development of tumor, thus acting as an oncogene. In the second part of this work, the expression of 10 long non-coding RNAs (lncRNAs) was analyzed against the same lineage panel described above. Among these, the LINC01133 lncRNA exhibited low expression levels in the non-tumorigenic MCF10A and MCF12A lineages and high levels in the triple negative Hs578T lineage, being, then, chosen as a target for this study. Based on these results, we decided toinducibly overexpress LINC01133 in the MCF10A lineage and knockout this gene, via the CRISPR/Cas9 system, in the Hs578T lineage. Functional characterization assays showed that overexpression of LINC01133 in the MCF10A lineage reduced cell proliferation and inhibited anchorage-dependent colony growth, but, on the other hand, increased anchorage-independent colony growth and the migratory and invasive capacity of these cells. However, we suggest that this is not sufficient to render these cells tumorigenic and metastatic. On the other hand, the knockout of LINC01133 in the triple negative Hs578T lineage considerably increased all the analyzed malignancy parameters. Based on the results obtained, we suggest that the high expression level of LINC01133 in the Hs578T lineage is important for down-regulation of processes related to tumor progression, acting as a tumor suppressor. The data obtained in our study contribute to the enrichment of information related to TNBC Biology, thus assisting in the development of potential clinical and therapeutic protocols using these biomarkers

LncRNA PCAT-1 Reduces Sensitivity of Cervical Carcinoma Cells to Cisplatin by Regulating STAT3 and PTEN Expression / 肿瘤防治研究

Objective To investigate the role and regulatory mechanism of lncRNAs PCAT-1 in the sensitivity of cervical cancer cells to DDP. Methods The expressions of PCAT-1 in human cervical cancer cell lines (HeLa and SiHa) and DDP-resistant cell lines (HeLa/DDP and SiHa/DDP) were analyzed by real-time PCR. After PCAT-1 silencing and overexpression in HeLa/DDP and SiHa/DDP cells, CCK-8 and flow cytometry were used to detect cell viability ability and cell cycle, respectively. Western blot was used to detect the protein expression of STAT3 and PTEN. Results The DDP resistance index of HeLa/DDP cells to HeLa cells was 4.49, while that of SiHa/DDP cells to SiHa cells was 6.87. The expression levels of PCAT-1 in HeLa/DDP and SiHa/DDP cells were significantly higher than those in HeLa and SiHa cells, respectively (P < 0.05). The overexpression of PCAT-1 reduced the sensitivity of HeLa/DDP and SiHa/DDP cells to DDP, enhanced the proportion of S phase in cell cycle, and decreased the proportion of G0-G1 and G2-M phases (P < 0.05). The silencing of PCAT-1 increased the sensitivity of HeLa/DDP and SiHa/DDP cells to DDP, decreased the proportion of S phase in the cell cycle, and enhanced the proportion of G0-G1 and G2-M phase (P < 0.05). Overexpression of PCAT-1 promoted STAT3 protein expression but inhibited PTEN protein expression in HeLa/DDP and SiHa/DDP cells (P < 0.05). The silencing of PCAT-1 inhibited STAT3 protein expression but promoted PTEN protein expression in HeLa/DDP and SiHa/DDP cells (P < 0.05). Conclusion PCAT-1 is upregulated in HeLa/DDP and SiHa/DDP cells. PCAT-1 reduces the sensitivity of HeLa/DDP and SiHa/DDP cells to DDP by upregulating the expression of STAT3 and downregulating the expression of PTEN.

Abnormally expressed lncRNAs in the prognosis and clinicopathology of oesophageal cancer: a systematic review and meta-analysis

The relationship between the long noncoding RNA (lncRNA) expression and oesophageal cancer prognosis has been widely studied, but less consensus has been reached. We conducted this study to evaluate the relationship between the expression of lncRNAs and the prognosis and clinical pathology of oesophageal cancer. We conducted a systematic search of PubMed, EMBASE and Cochrane Library until 25 January 2019. Studies that evaluated the associations of a specific lncRNA with survival and/or clinicopathology of oesophageal cancer were included. Pooled hazard ratios (HRs), odds ratios (ORs), and corresponding 95% confidence intervals (CIs) were calculated using fixed or random-effect models. Sensitivity analysis was used to verify the stability of results. Publication bias was detected using Begg tests and adjusted utilizing the trim-and-fill method if a bias existed. A total of 51 studies comprising 6510 patients and regarding 41 lncRNAs were included in the present systematic review and meta-analysis. The results showed that dysregulation of lncRNAs was associated with overall survival, disease-free survival, and progression-free survival. The expression of lncRNAs was related to some certain clinicopathological parameters of oesophageal cancer, including tumour size, T classification, lymph node metastasis, tumour node metastasis (TNM) stage and differentiation. Among these findings, lncRNA AK001796, CASC9, HOTAIR, MALAT1 and UCA1 were identified and were expected to be ideal biomarkers for the prognosis and clinicopathology of oesophageal cancer. Although significant publication bias was observed in some studies, the results were not changed after adjustment using the trim-and-fill method. Abnormal lncRNA-expression profiles could serve as a promising indicator for prognostic evaluation of patients with oesophageal cancer. The combination of these lncRNAs will contribute to clinical decision-making in the future.

Advances of long noncoding RNAs in myocardial fibrosis / 中国药科大学学报

@#Accumulating studies have recently shown that long noncoding RNAs (lncRNAs) are involved in the initiation and progression of myocardial fibrosis,a common histological characteristic of heart conditions and prominent global health issues. LncRNAs are prominently served as regulatory molecules via interaction with DNA,RNA and proteins in transcriptional and post-transcriptional processes. They can change morphological structure and biochemical metabolism of cardiac cells and regulate homeostasis of the cardiac extracellular matrix. Therefore,lncRNAs show great potential as diagnostic and prognostic biomarkers and therapeutic targets for anti-fibrotic treatment.

Non-coding rnas in human dental pulp stem cells: Regulations and mechanisms / 中国组织工程研究

BACKGROUND: Human dental pulp stem cells are important oral mesenchymal stem cells with strongproliferation and multidirectional differentiation functions. In-depth studies on the Human Genome Project make people gradually reali ze that functional non-coding RNAs play an extraordinary role in regulating gene expression. OBJECTIVE: To discuss the function and application of non-coding RNAs in human dental pulp stem cells. METHODS: Using “ncRNAs, human dental pulp stem cells, regenerative medicine” as keywords in English and Chinese, the first author searched PubMed, Medline, CNKI, and WanFang for relevant articles published from 2005 to 2019. Literatures unrelated to the purpose of the study and repetitive literatures were excluded, and 71 articles that meet the criteria were included for review. RESULTS AND CONCLUSION: It is now generally believed that non-coding RNAs can be used as a signal of specific cell state, providing prognostic value and even providing treatment options for patients. With the continuous development of regenerative medicine applications, human dental pulp stem cells are arousing increasing attentions. Exploration on the relationship between non-coding RNAs and human dental pulp stem cells provides a new approach for the clinical application of human dental pulp stem cells.

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.

Research Advances in the Effect of Mechanical Regulation of Long-Chain Non-Coding RNAs on Osteogenic Differentiation of Mesenchymal Stem Cells / 医用生物力学

With the development of the 3rd-generation high-throughput sequencing technology and tissue engineering, recent studies show that many long-chain non-coding RNAs (LncRNAs) have played an important role in osteogenic differentiation of mesenchymal stem cells (MSCs). LncRNAs, which are involved in the regulation of mechanical regulation, further regulate bone-related cell functions and play a regulatory role at multiple levels, including transcription, post-transcriptional and epigenetic. LncRNAs may be involved in the osteogenic differentiation and bone remodeling of MSCs, the regulation of bone-related cell functions as a mechanical response molecule, as well as the pathological process of skeletal diseases.

Biologia de Sistemas de RNAs Não-Codificadores Longos na Vacinação / Systems biology of Long Non-Coding RNAs in vaccination

Entender os mecanismos responsáveis pela proteção induzida por vacinas contribui para o desenvolvimento de novas vacinas. Uma abordagem de pesquisa denominada Vacinologia de Sistemas surgiu para endereçar essa tarefa. A aplicação da Vacinologia de Sistemas gerou informações amplas relacionadas a respostas vacinais e foi aplicada no estudo de diversas vacinas. Apesar de estarem envolvidos em diversos processos imunológicos, RNAs Não-Codificadores Longos (lncRNAs) ainda não foram estudados no contexto da imunidade induzida por vacinas. Neste trabalho, fizemos a análise de mais de 2.000 amostras de transcritoma de sangue periférico, oriundas de 17 diferentes coortes vacinadas, com foco na identificação de lncRNAs potencialmente envolvidos com a resposta induzida por vacinas contra gripe e contra febre amarela. Criamos também um banco de dados online, em que todos os nossos resultados podem ser facilmente acessados. Nossos resultados indicaram que diversos lncRNAs participam de múltiplas vias imunológicas relacionadas a respostas induzidas por vacinas. Entre esses, o transcrito FAM30A se destaca por ter alta expressão em células B e ser correlacionado com a expressão de genes de imunoglobulina localizados no mesmo locus genômico. Identificamos também alterações na expressão de lncRNAs em dados de RNA-seq de uma coorte de crianças imunizadas com uma vacina atenuada contra gripe, o que sugere um papel de lncRNAs na resposta a diferentes vacinas. Nossos achados trazem evidências de que lncRNAs tem um papel significativo na resposta imune induzida por vacinas

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of Systems Vaccinology provides detailed information on host responses to vaccination and has been successfully applied in the study of the molecular mechanisms of several vaccines. Long Non-Coding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from these analyses can be easily accessed. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children vaccinated with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination

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.

MicroRNAs and lncRNAs in psoriasis / 中华皮肤科杂志

Psoriasis is a common chronic inflammatory skin disease,and commonly considered as a T cell-mediated abnormal immune disease with genetic predisposition at present.Recent studies have indicated that microRNAs and lncRNAs play important roles in occurrence and development of a variety of inflammatory immune diseases.It has been confirmed that microRNAs and lncRNAs participate in the occurrence of psoriasis by regulating the proliferation and differentiation of keratinocytes,release of inflammatory factors,and angiopoiesis.This review summarizes research advances in roles of microRNAs and lncRNAs in psoriasis.

lincRNA-p21 and malignant tumors of digestive system / 中国肿瘤生物治疗杂志

@# 基因间的长链非编码RNA-p21（long intergenic non-coding RNA，lincRNA-p21）是lncRNAs中的一种，可通过发挥多种 生物学功能影响肿瘤的增殖、转移、侵袭，并且对放、化疗的敏感度产生影响。lincRNA-p21在胃癌、肝癌、结直肠癌的进展中充当 肿瘤抑制基因；也有研究发现lincRNA-p21在常氧条件下无抑癌作用，而在乏氧条件下能抑制乏氧肿瘤细胞增殖；其能够通过抑 制β-连环蛋白信号转导的活性，从而降低肿瘤干细胞的体外活性。因此，lincRNA-p21有望成为一种新型肿瘤生物标志物，在肿 瘤的早期诊断、治疗及预后评估等方面具有重要潜在价值。本文对lincRNA-p21在消化系统恶性肿瘤中作用的研究进展作一 综述。

LncRNA-HCG11 affects progression and metastasis of colorectal cancer via regulating miR-144-3p/ZEB1 axis / 中国肿瘤生物治疗杂志

@#To investigate the molecular mechanism of lncRNA-HCG11 promoting progression and metastasis of colorectal cancer (CRC) via up-regulating zinc finger E box binding homeobox 1 (ZEB1) by regulating miR-144-3p expression in CRC. Methods:Atotal of 78 pairs of CRC tissues and corresponding adjacent tissues were obtained from patients in Department of Colorectal Surgery, Cancer Hospital of Yunnan Province during January 2013 and January 2018. HCG11 expression level in CRC cell lines and tissues was determined by qPCR; HCG11-knockdown vector, miR-144-3p mimic and miR-144-3p inhibitor were constructed and transfected into CRC cells lines (SW480 and SW620); and then, cell viability was detected by using CCK-8 assay and colony formation assay, while cell migration and invasion was assessed by using transwell assay; the expression levels of ZEB1 and epithelial mesenchymal markers (E-cadherin, Vimentin, ɑ-catenin, Sox2, Nestin, Oct4 and Nanog) were detected by Wb and immunofluorescence assay; and the relationship between HCG11, miR-144-3p and ZEB1 was validated by dual-luciferase reporter gene assay. Nude mice xenograft model was constructed and the effect of HCG11 knock-down on the growth of xenograft was evaluated. Results: The expression of HCG11 was significantly higher in CRC cell lines (all P<0.05) and tissues (P<0.01) compared with that in normal colon epithelial cells and para-cancerous tissues; HCG11 expression was closely related with cancer metastasis, clinical staging and prognosis of CRC patients (all P<0.05). Knockdown of HCG11 significantly inhibited cells proliferation, migration, invasion, epithelial-mesenchymal transition and CRC stem cell formation (all P<0.05). Moreover, knockdown of HCG11 significantly up-regulated miR-144-3p expression (P<0.05), while over-expression of miR-144-3p significantly inhibited ZEB1 expression (P<0.05) and reduced dual-luciferase activity (P＜0.05). Conclusion: HCG11 regulates miR-144-3p to up-regulate ZEB1 expression, and further promotes CRC progression and metastasis; therefore, HCG11 could be used as a target for clinical diagnosis and treatment for CRC.

Hepatocellular carcinoma-related lncRNAs in different human races in the TCGA database: Screening and prediction of their functions / 医学研究生学报

Objective Differentially-expressed lncRNAs in hepatocellular carcinoma (HCC) among different races remain unclarified at present time. This study aimed to analyze the shared and specific differential expression profiles of lncRNAs in HCC patients of the yellow, white and black races in the TCGA database and predict their functions and regulatory mechanisms. Methods We screened differentially expressed lncRNAs in the cancer and paracancer tissues of the HCC patients of the yellow, white and black races, compared differential expression profiles of lncRNAs and identified the common differentially expressed lncRNAs among the three races. We performed COX regression survival analysis on the differentially expressed lncRNAs, constructed a ceRNA network, and predicted the target genes and their regulatory mechanisms by GO and KEGG enrichment analyses and prediction of the transcription factors. Results Totally 49 HCC-related lncRNAs were found in all the three races, with 21.5% overlapped in the white and black races, 7.8% in the white and yellow and 5.8% in the black and Asians. GO enrichment analysis showed that the target genes of LINC01224 in the all three races were related to DNA replication and transposition, gene expression regulation, epigenetics, silencing of miRNAs, and gene silencing after RNA transcription, while KEGG analysis revealed a correlation of LINC01224 with the cell cycle and DNA replication. Target genes were not predicted in the 11 survival-related lncRNAs in the patients of the white race. Of the 6 survival-related lncRNAs in the yellow patients, the target gene of AC093609.1 was shown to be involved in the activity of the ionic channel, regulation of cardiomyopathy- and cardiomyocyte adrenalin-related signaling pathways, various metabolic functions, fat degradation, ABC protein transportation, and amino acid metabolism. Conclusion HCC-related expression profiles of lncRNAs have a great similarity between the white and black races, but a high differentiality between the yellow and the white or black. LINC01224 may be involved in the relation of tumor growth in all the three races, while AC093609.1 and AC126118.1 specific of the yellow race play an important role in tumor metabolism.

Role of LncRNAs in cell senescence and therapeutic targets / 中国药理学通报

Long non-coding RNAs (LncRNAs) are non-coding RNAs with a length of more than 200 bp. Cellular senescence is a stable proliferative stagnation state, which is irreversible and may be caused by a variety of factors, such as telomere shortening, oncogene induction or oxidative stress. Multiple factors are involved in cellular senescence, in which p53/p21 and pl6/Rb are major regulators of cellular senescence in different cell types. Cellular aging has been extensively studied as a powerful tumor suppressor mechanism to counter the emergence of oncogenes. In this review, the mechanism of action and therapeutic targets of LncRNAs in senescent cells are explored in depth.

LncRNAs in CONDBITs Perspectives, From Genetics towards Theranostics / Jurnal Sains Kesihatan Malaysia

@#LncRNAs (Long noncoding RNAs) are novel group of ncRNAs and has been discovered to be pervasively transcripted in the genome, characterized as endogenous cellular RNAs consist of more than 200 nucleotides. They are ordered in view of function, transcript length, relation with protein-coding genes and other functional DNA elements, and subcellular localization. Theranostics is a novel study in medicine that combines specific targeted biomolecules based upon molecular-based test. As novel finding in the field of molecular medicine, lncRNA is indispensable tools in theranostics based medicine that allows specific targeting of molecular pathway for diagnostics and therapeutics. LncRNAs may execute as signals, decoys, guides, and scaffolds in their natural capacities. LncRNA expression is controlled by transcriptional and epigenetic factors and processes. LncRNAs also relate detracting biological programs. Here we reviewed lncRNAs in disorders/diseasest horoughly based on CONDBITs perspectives, i.e.: cardiology, oncology, neurology and neuroscience, dermatology, the biology of molecular and bioinformatics, immunology, and technologies (related with “-omics”; transcriptomics and “nano”; nanotechnology). It was narrated the lncRNA biomarkers that abundant in cardiovascular, neurodegenerative, dermatology, and immunology perspective. However, as cancer is the most widely studied disease, more biomarkers are available for this particular case. There are abundant cancer-associated lncRNAs. The most frequent learned lncRNA molecules in cancer are HOTAIR, MALAT1, LincRNA-p21, H19, GAS5, ANRIL, MEG3, XIST, HULC. LncRNAs in cancer diagnosis and monitoring, e.g.: H19 and AA174084 (gastric), HULC (hepatocellular), PCA3 (prostate). Prognostic lncRNAs, e.g.: HOTAIR and NKILA (breast), MEG3 (meningioma), NBAT-1 (neuroblastoma), SCHLAP1 (prostate). LncRNAs predicting therapeutic responsiveness, e.g.: CCAT1 (colorectal), HOTAIR (ovarian). Thus, it is concluded that the CONDBIT perspective is useful to describe the encouraging outlook of this transcriptomics-based medicinal approach.