lncRNA XLOC Research Articles

Abstract 3567: A novel E2F1-regulated lncRNA, XLOC_000190, is required for S phase progression and cell proliferation

Abstract Long non-coding RNAs (lncRNAs) are major regulators of many cellular processes including cell cycle progression and cell proliferation. The pivotal transcription factor E2F1 induces both proliferation and cell death and is a critical downstream target of the tumor suppressor RB. The RB/E2F pathway is often inactivated in human tumors resulting in deregulated E2F activity. Here, we report that the human lncRNA XLOC_000190 is an E2F1- regulated lncRNA that plays a role in S phase progression. XLOC_000190 levels are elevated upon activation of E2F1. Furthermore, knockdown of E2F1 and E2F3 reduce XLOC_000190 levels and endogenous E2F1 binds the XLOC_000190 promoter. Moreover, expression of XLOC_000190 is cell cycle regulated and peaks near G1/S transition and in early S. Inhibition of XLOC_000190 expression increases percentage of S phase cells, suggesting that XLOC_000190 plays a role in S phase progression. Also, silencing of XLOC_000190 in cells that are synchronized at the G1/S delays progression of cells through S phase. In agreement with its suggested role in S phase, prolonged silencing of XLOC_000190 inhibits proliferation of human cancer cells in culture. XLOC_000190 is a nuclear lncRNA and its gene is localized downstream to the protein-coding gene CDKN2C that encodes the p18ink4c CDK inhibitor. In search for XLOC_000190 mode of action we do not detect any changes in the expression of this neighbor upon XLOC_000190 silencing. However, XLOC_000190 silencing leads to a significant decrease in the level of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), which is a critical player in S phase progression. Additional data indicate that RRM2 mediates, at least in part, the effect of XLOC_000190 on S phase progression. Importantly, low levels of XLOC_000190 are associated with increased survival of kidney cancer patients. In conclusions, our data identify XLOC_000190 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation, at least in part, via regulation of RRM2. Citation Format: Doron Ginsberg, Tali Nizri-Megnaji, Esther Baruch. A novel E2F1-regulated lncRNA, XLOC_000190, is required for S phase progression and cell proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3567.

Transcriptomic analysis between Normal and high-intake feeding geese provides insight into adipose deposition and susceptibility to fatty liver in migratory birds

BackgroundDysregulation of adipogenesis causes metabolic diseases, like obesity and fatty liver. Migratory birds such as geese have a high tolerance of massive energy intake and exhibit little pathological development. Domesticated goose breeds, derivatives of the wild greyleg goose (Anser anser) or swan goose (Anser cygnoides), have high tolerance of energy intake resembling their ancestor species. Thus, goose is potentially a model species to study mechanisms associated with adipogenesis.ResultsPhenotypically, goose liver exhibited higher fat accumulation than adipose tissues during fattening (liver increased by 3.35 fold than 1.65 fold in adipose), showing a priority of fat accumulation in liver. We found the number of differentially expressed genes in liver (13.97%) was nearly twice the number of that in adipose (6.60%). These differentially expressed genes in liver function in several important lipid metabolism pathways, immune response, regulation of cancer, while in adipose, terms closely related to protein binding, gluconeogenesis were enriched. Typically, genes like MDH2 and SCD, which have key roles in glycolysis and fatty acids metabolism, had higher fold change in liver than in adipose tissues. Three hundred two differentially expressed long noncoding RNAs involved in regulation of metabolism in liver were also identified. For example, lncRNA XLOC_292762, which was 5.7 kb downstream of FERMT2, a gene involved phosphatidylinositol-3,4,5-trisphosphate binding, was significantly down-regulated after the high-intake feeding period. Further investigation of documented obesity-related orthologous genes in goose suggested that understanding the evolutionary split from mammals in adipogenesis will make goose fatty liver a better resource for future research.ConclusionsOur research reveals that goose uses liver as the major tissue to regulate a distinct lipid synthesis and degradation flux and the dynamic expression network analyses showed numerous layers of positive responses to both massive energy intake and possible pathological development. Our results offer insights into goose adipogenesis and provide a new perspective for research in human metabolic dysregulation.

A Novel lncRNA Regulates the Toll-Like Receptor Signaling Pathway and Related Immune Function by Stabilizing FOS mRNA as a Competitive Endogenous RNA.

Long non-coding RNAs (lncRNAs) have recently emerged as new regulatory molecules with diverse functions in regulating gene expression and significant roles in the immune response. However, the function of many unknown lncRNAs is still unclear. By studying the regulatory effect of daidzein (DA) on immunity, we identified a novel lncRNA with an immune regulatory function: lncRNA- XLOC_098131. In vivo, DA treatment upregulated the expression of lncRNA- XLOC_098131, FOS, and JUN in chickens and affected the expression of activator protein 1 (AP-1) to regulate MAPK signaling, Toll-like receptor signaling, and related mRNA expression. It also enhanced macrophage activity and increased the numbers of blood neutrophils and mononuclear cells, which can improve the body's ability to respond to stress and bacterial and viral infections. Furthermore, DA treatment also reduced B lymphocyte apoptosis and promoted the differentiation of B lymphocytes into plasma cells, which in turn resulted in the production of more immunoglobulins and the promotion of antigen presentation. In vitro, using HEK293FT cells, we demonstrated that mir-548s could bind to and decrease the expression of both FOS and lncRNA- XLOC_098131. LncRNA- XLOC_098131 served as a competitive endogenous RNA to stabilize FOS by competitively binding to miR-548s and thereby reducing its inhibitory effect of FOS expression. Therefore, we concluded that the novel lncRNA XLOC_098131 acts as a key regulatory molecule that can regulate the Toll-like receptor signaling pathway and related immune function by serving as a competitive endogenous RNA to stabilize FOS mRNA expression.

An Integrated Analysis of Cashmere Fineness lncRNAs in Cashmere Goats.

Animal growth and development are regulated by long non-coding RNAs (lncRNAs). However, the functions of lncRNAs in regulating cashmere fineness are poorly understood. To identify the key lncRNAs that are related to cashmere fineness in skin, we have collected skin samples of Liaoning cashmere goats (LCG) and Inner Mongolia cashmere goats (MCG) in the anagen phase, and have performed RNA sequencing (RNA-seq) approach on these samples. The high-throughput sequencing and bioinformatics analyses identified 437 novel lncRNAs, including 93 differentially expressed lncRNAs. We also identified 3084 differentially expressed messenger RNAs (mRNAs) out of 27,947 mRNAs. Gene ontology (GO) analyses of lncRNAs and target genes in cis show a predominant enrichment of targets that are related to intermediate filament and intermediate filament cytoskeleton. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, sphingolipid metabolism is a significant pathway for lncRNA targets. In addition, this is the first report to reveal the possible lncRNA–mRNA regulatory network for cashmere fineness in cashmere goats. We also found that lncRNA XLOC_008679 and its target gene, KRT35, may be related to cashmere fineness in the anagen phase. The characterization and expression analyses of lncRNAs will facilitate future studies on the potential value of fiber development in LCG.

Decreased expression of long noncoding RNA XLOC_013703 promotes cell growth via NF-κB pathway in multiple myeloma.

Long noncoding RNAs (lncRNAs) are dysregulated in cancer and involved in oncogenic or tumor inhibitory processes. The aim of the study was to investigate the expression pattern of lncRNA XLOC_013703 in multiple myeloma (MM) and to evaluate its biological role and potential significance. We found that XLOC_013703 was significantly decreased in CD138 positive plasma cells and serum of MM patients compared to normal controls, and the decreased XLOC_013703 expression was correlated with β2-MG, serum-free light chain (s-FLC) and revised international staging system. RNA-fluorescence in situ hybridization results revealed that XLOC_013703 was distributed both in the nucleus and in the cytoplasm of MM cells including H929, RPMI8226, and U266. Overexpression of XLOC_013703 inhibited the proliferation of U266 cells and blocked the cell cycle in G1 stage, thus contributing to MM cell apoptosis. By contrast, knockdown of XLOC_013703 promoted the growth of H929 cells. Western blot analysis confirmed that the expression of p-IκBα and nuclear P65 was substantially increased in shRNA transfection groups compared to control groups, whereas overexpression of XLOC_013703 reduced these expressions. In conclusion, we confirmed that the decreased expression of a novel lncRNA, XLOC_013703, in MM. XLOC_013703 was involved in MM cell survival and proliferation via nuclear factor-κB pathway which represents a potential therapeutic target for MM. © 2019 IUBMB Life, 71(9):1240-1251, 2019.

Genome‑wide profiling of lncRNA and mRNA expression in CRSwNP.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most prevalent chronic diseases. In patients with CRSwNP, the present study performed comprehensive bioinformatics analyses to characterize the transcriptome profiles of mRNAs and long non‑coding RNAs (lncRNAs). A total of 265differentially expressed lncRNAs and 994mRNAs were identified. The majority of up‑ and downregulated differentially expressed genes were significantly enriched in the biological process of 'signal transduction'. The most significantly enriched molecular function was 'protein binding' and the most significantly enriched cellular component was 'membrane'. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis led to identification of several significantly enriched pathways [false discovery rate (FDR)<0.05], including 'cytokine‑cytokine receptor interaction' (FDR=3.94x1016) and 'cell adhesion molecules' (CAMs) (FDR=1.28x10‑5). Key differentially expressed lncRNAs were identified, including lncRNA XLOC_010280, which regulates chemokine (C‑C motif) ligand 18 (CCL18) and inflammation, and RP11‑798M19.6, which regulates polypeptide N‑acetylgalactosaminyltransferase7 (GALNT7) and cell proliferation. Based on the results of reverse transcription‑quantitative polymerase chain reaction, except for CCL8, neural precursor cell expressed developmentally downregulated gene 4‑like and GALNT7, the expression of 3other selected genes was consistent with the results of integrated analysis. The results of the present study provide a foundation for future investigations into mRNAs and lncRNAs as diagnostic and therapeutic targets in CRSwNP.

LncRNAs in polyploid cotton interspecific hybrids are derived from transposon neofunctionalization

BackgroundInterspecific hybridization and whole genome duplication are driving forces of genomic and organism diversification. But the effect of interspecific hybridization and whole genome duplication on the non-coding portion of the genome in particular remains largely unknown. In this study, we examine the profile of long non-coding RNAs (lncRNAs), comparing them with that of coding genes in allotetraploid cotton (Gossypium hirsutum), its putative diploid ancestors (G. arboreum; G. raimondii), and an F1 hybrid (G. arboreum × G. raimondii, AD).ResultsWe find that most lncRNAs (80%) that were allelic expressed in the allotetraploid genome. Moreover, the genome shock of hybridization reprograms the non-coding transcriptome in the F1 hybrid. Interestingly, the activated lncRNAs are predominantly transcribed from demethylated TE regions, especially from long interspersed nuclear elements (LINEs). The DNA methylation dynamics in the interspecies hybridization are predominantly associated with the drastic expression variation of lncRNAs. Similar trends of lncRNA bursting are also observed in the progress of polyploidization. Additionally, we find that a representative novel lncRNA XLOC_409583 activated after polyploidization from a LINE in the A subgenome of allotetraploid cotton was involved in control of cotton seedling height.ConclusionOur results reveal that the processes of hybridization and polyploidization enable the neofunctionalization of lncRNA transcripts, acting as important sources of increased plasticity for plants.

Circulating lncRNA XLOC_009167 serves as a diagnostic biomarker to predict lung cancer

BackgroundLong noncoding RNAs (lncRNAs) have been proven to be involved in carcinogenesis and to be released into peripheral blood. Our objective was to develop a circulating lncRNA as a novel biomarker to predict lung cancer. MethodsWe analyzed the lncRNA expression profile in lung cancer patients by lncRNA array and identified lncRNA XLOC_009167 as a circulating biomarker using qRT-PCR in whole blood of lung cancer patients. The diagnostic value of was analyzed by area under curve (AUC) and the receiver operating characteristic (ROC) test. ResultsLncRNA XLOC_009167 was screened as a candidate biomarker for lung cancer and was up-regulated in both lung cancer tissues and cell lines. Notably, lncRNA XLOC_009167 in whole blood of lung cancer patients was highly expressed as compared with that in healthy controls or in patients with pneumonia. The values of AUC of lung cancer vs. healthy controls, and that of lung cancer vs. pneumonia were 0.7398 (95%CI = 0.6493 to 0.8303) and 0.7005 (95%CI = 0.5771 to 0.8240), respectively. Intriguingly, the ROC showed lncRNA XLOC_009167 was a better diagnostic potential compared to the traditional biomarkers (CYFR21-1, NSE and CA72-4), and the circulating lncRNA XLOC_009167 was found to be stable in whole blood under different conditions. ConclusionsLncRNA XLOC_009167 could serve as a novel diagnostic biomarker to distinguish lung cancer from benign lung disease and healthy controls.

RNA-seq analysis of lncRNA-controlled developmental gene expression during puberty in goat & rat

BackgroundPuberty is a pivotal stage in female animal development, and marks the onset of reproductive capability. However, little is known about the function of lncRNAs (long noncoding RNAs) in puberty. Therefore, RNA-seq analysis were performed between goats and rats to clarify the roles of lncRNAs and mRNAs in the onset of puberty.ResultsIn the present study, the length of lncRNAs, the length of the open reading frame and the exon count were compared between the two species. Furthermore, functional annotation analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis of lncRNAs target genes and differentially expressed mRNA demonstrated the significantly enriched terms, such as AMPK signaling pathway, oxytocin signaling pathway, insulin secretion as well as pheromone receptor activity, and some other signaling pathways which were involved in the regulation of female puberty. Moreover, our results of siRNA interference in vitro showed the candidate lncRNA XLOC_446331 may play a crucial role in regulating female puberty.ConclusionIn conclusion, the RNA-seq analysis between goat and rat provide novel candidate regulators for genetic and molecular studies on female puberty.

Downregulation of the long non-coding RNA XLOC_010588 inhibits the invasion and migration of colorectal cancer.

Long non-coding RNAs (lncRNAs) have emerged as major players in many biological and pathological processes; however, investigation into the function of lncRNAs in the development and progression of cancer is in its infancy. Therefore, clarification of the mechanism by which cancer-related lncRNAs function is of critical importance in research on tumorigenesis. It has been demonstrated that the lncRNA XLOC_010588 is expressed at a low level in cervical cancer, and that this has significant impact on the proliferation of cervical cancer cells. However, the expression pattern and functional roles of XLOC_010588 in colorectal cancer (CRC) remain unclear. In the present study, it was demonstrated that the expression of XLOC_010588 was significantly higher in CRC tissues when compared with that in adjacent normal tissues, and that XLOC_010588 was closely associated with metastasis and poor prognosis, thus indicating that XLOC_010588 may function as an oncogene. Additionally, downregulation of XLOC_010588 expression markedly inhibited the invasion and migration of CRC cells. Furthermore, it was demonstrated that XLOC_010588 may regulate the progression of CRC via the epithelial-mesenchymal transition (EMT) pathway. Notably, downregulation of XLOC_010588 inhibited the invasion and migration of CRC cells by regulating genes associated with EMT. Our findings revealed that XLOC_010588 may be considered as a novel potential diagnostic biomarker in CRC.

LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a ceRNA against miR-331-3p and miR-338-3p.

ObjectiveCervical cancer is one of the most common malignant tumors. Our previous results showed that long non-coding RNA (lncRNA) XLOC_006390 plays an important role in cervical cancer. In this study, we have explored the mechanism of action of lncRNA XLOC_006390.MethodsLncRNA XLOC_006390 was proposed to exercise its function as a competing endogenous RNA (ceRNA), and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. Two miRNAs, miR-331-3p, and miR-338-3p, were chosen for the study. Expression of miRNAs and lncRNA in cervical cancer cells and tissues was detected by reverse transcription polymerase chain reaction. To determine the correlation, silencing of XLOC_006390, over-expression of miR-331-3p, and miR-338-3p was performed in SiHa and Caski cell lines, respectively.ResultsBased on the interactive effect between miRNA and lncRNA, miR-331-3p and miR-338-3p were significantly downregulated in cervical cancer cells and tissues, and their expression levels were negatively related to that of lncRNA. Our results also showed that the expression of miR-331-3p target gene NRP2, miR-338-3p target genes PKM2, EYA2 was significantly downregulated when the XLOC_006390 was knocked down. Further, XLOC_006390 was found to facilitate cervical cancer tumorigenesis and metastasis by downregulating miR-331-3p and miR-338-3p expression.ConclusionTaken together, our study demonstrated that XLOC_006390 may serve as a ceRNA and reversely regulates the expression of miR-331-3p and miR-338-3p, thus facilitating cervical cancer tumorigenesis and metastasis.

Long non-coding RNA XLOC_008466 acts as an oncogenic molecular in cervical cancer tumorigenesis

Cervical cancer is one of the most common malignant carcinomas in the female reproductive system. Long non-coding RNAs (lncRNAs) have been verified to participate in the tumorigenesis of cervical cancer. In present study, we investigate the role of lncRNA XLOC_008466 in the occurrence and progression of cervical cancer. Results showed that XLOC_008466 expression was up-regulated in cervical cancer tissue and cells compared to normal controls. In vitro functional experiments, CCK-8 assay and colony formation assay showed that XLOC_008466 knockdown suppressed the proliferation of cervical cancer cells. Flow cytometry and transwell assay showed that XLOC_008466 knockdown induced G0/G1 phase arrest and aggravated the apoptosis. In vivo, XLOC_008466 knockdown inhibited the tumor growth. Bioinformatics analysis revealed that XLOC_008466 sponged miR-216b with the complementary binding sites at 3’-UTR. Overall, our study reveals the tumor promoting role of XLOC_008466 in cervical cancer carcinogenesis, providing a novel molecular mechanism and therapeutic target for cervical cancer.

Up-regulation of long non-coding RNA XLOC_010235 regulates epithelial-to-mesenchymal transition to promote metastasis by associating with Snail1 in gastric cancer

We previously performed long non-coding RNA (lncRNA) expression microarray analyses to identify novel indicators for gastric cancer (GC) metastasis and prognosis in which we identified lncRNA XLOC_010235 (XLOC) as a candidate RNA. However, XLOC_010235 molecular mechanism of action remains unclear. Gain and loss of function approaches were used to investigate the biological role of XLOC in vitro. The effects of XLOC on cell viability were assessed by CCK-8 proliferation assays. Real-time PCR, western-blot and immunofluorescence were used to evaluate the mRNA and protein expression of Snail and multiple EMT related molecules. The positive XLOC/Snail1 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. Ectopic expression of XLOC facilitate cell viability, migration and invasion, leading to the acceleration of metastasis, while depletion of XLOC expression hindered cell migration and invasion. Moreover, over-expression of XLOC was found to play a important role in epithelial-to-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression, in which transcriptional factor Snail1 was involved. These results advance our understanding of the role of lncRNA XLOC_010235 as a active regulator of EMT by associating with Snail1, which may help in the development of new therapeutics.

Deregulated lncRNAs in B Cells from Patients with Active Tuberculosis.

Role of lncRNAs in human adaptive immune response to TB infection is largely unexplored. To address this issue, here we characterized lncRNA expression profile in primary human B cell response to TB infection using microarray assay. Several lncRNAs and mRNAs were chosen for RT-qPCR validation. Bioinformatics prediction was applied to delineate function of the deregulated mRNAs. We found that 844 lncRNAs and 597 mRNAs were differentially expressed between B cell samples from individuals with or without TB. KEGG pathway analysis for the deregulated mRNAs indicated a number of pathways, such as TB, TLR signaling pathway and antigen processing and presentation. Moreover, corresponding to the dysregulation of many lncRNAs, we also found that their adjacent protein-coding genes were also deregulated. Functional annotation for the corresponding mRNAs showed that these lncRNAs were mainly associated with TLR signaling, TGF-β signaling. Interestingly, SOCS3, which is a critical negative regulator of cytokine response to TB infection and its nearby lncRNA XLOC_012582, were highly expressed in active TB B cells. Subsequent RT-qPCR results confirmed the changes. Whether upregulated XLOC_012582 causes SOCS3 overexpression and is eventually involved in the context of exacerbations of active TB represents an interesting issue that deserves to be further explored. Taken together, for the first time, we identified a set of deregulated lncRNAs in active TB B cells and their functions were predicted. Such findings provided novel insight into the pathogenesis of TB and further studies should focus on the function and pathogenic mechanisms of the lncRNAs involved in active TB.

Long non-coding RNA XLOC_006390 promotes cervical cancer proliferation and metastasis through the regulation of SET domain containing 8.

The long non-coding RNA (lncRNA) XLOC_006390 is increased in various human cancer tissues and it plays important roles in cell growth and migration. However, the role of lncRNA XLOC_006390 in the progression and metastasis of cervical cancer has not been evaluated and remains unclear. In the present study, we hypothesized that lncRNA XLOC_006390 is also increased in cervical cancer, and upregulation of lncRNA XLOC_006390 contributes to cervical cancer metastasis. The expression of lncRNA XLOC_006390 in cervical cancer tissues and cell lines was analyzed using quantitative reverse-transcription-polymerase chain reaction (qRT-PCR). RNA interference approach and an overexpression system were used to investigate the cellular functions of XLOC_006390 and SET domain containing8 (SET8). Cell Counting Kit-8 (CCK-8) assay was performed to detect cell proliferation. Cell migration and invasion abilities were evaluated by Transwell assays. Western blotting and immunofluorescence were performed to detect SET8 protein expression. The results revealed that XLOC_006390 was increased in cervical cancer tissues. Patients with high XLOC_006390 expression were associated with FIGO stages IIIandIV (P=0.0170), lymphatic metastasis (P=0.0078) and distant metastasis (P=0.0025). Furthermore, SET8 was also increased in cervical cancer tissues and its expression was positively associated with XLOC_006390, and XLOC_006390 regulated SET8 expression. In addition, knockdown or overexpression of XLOC_006390 and SET8 expression suppressed or promoted cervical cancer cell proliferation, migration and invasion invitro, respectively. In conclusion, our data suggest that lncRNA XLOC_006390 promotes cervical cancer cell growth and metastasis through the regulation of SET8, at least partly, which indicate the critical roles of XLOC_006390 and SET8 in cervical cancer progression and metastasis.

Long Non-Coding RNA XLOC_008466 Functions as an Oncogene in Human Non-Small Cell Lung Cancer by Targeting miR-874

Background: The therapy and prognosis of lung cancer are difficult because of multiple genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) have been verified as new mediators of cancer development and progression by virtue of their various functions. Here, we focused on the lncRNA XLOC_008466 based on previous microarray data. However, whether aberrant expression of XLOC_008466 in human non-small cell lung cancer (NSCLC) is correlated with malignancy, metastasis or prognosis has not been elucidated. Methods: We performed real-time PCR, CCK-8, flow cytometry, trans-well, western blotting, luciferase reporter assays, RNA immunoprecipitation (RIP) assay and surface plasmon resonance (SPR) assay to detect the function of XLOC_008466 in NSCLC. Results: Up-regulation of XLOC_008466 in NSCLC patients was related to lymph node metastasis and the TNM stage. In vitro, down-regulation of XLOC_008466 inhibited cell proliferation and invasion of A549 and H460 cells in vitro, but promoted cell apoptosis. Experiments on mechanisms revealed that XLOC_008466 functioned as a ceRNA, directly binding to miR-874, and could affect cell proliferation, apoptosis and invasion through regulation of miR-874 expression as well as by increasing matrix metalloproteinase 2 (MMP2) and X-linked inhibitor of apoptosis (XIAP) expression. Conclusions: XLOC_008466 functions as an oncogene in NSCLC by regulating the miR-874-MMP2/XIAP axis, which indicates that XLOC_008466 may be a useful marker and potential therapeutic target in NSCLC.

LncRNA mediated regulation of aging pathways in Drosophila melanogaster during dietary restriction.

Dietary restriction (DR) extends lifespan in many species which is a well-known phenomenon. Long non-coding RNAs (lncRNAs) play an important role in regulation of cell senescence and important age-related signaling pathways. Here, we profiled the lncRNA and mRNA transcriptome of fruit flies at 7 day and 42 day during DR and fully-fed conditions, respectively. In general, 102 differentially expressed lncRNAs and 1406 differentially expressed coding genes were identified. Most informatively we found a large number of differentially expressed lncRNAs and their targets enriched in GO and KEGG analysis. We discovered some new aging related signaling pathways during DR, such as hippo signaling pathway-fly, phototransduction-fly and protein processing in endoplasmic reticulum etc. Novel lncRNAs XLOC_092363 and XLOC_166557 are found to be located in 10 kb upstream sequences of hairy and ems promoters, respectively. Furthermore, tissue specificity of some novel lncRNAs had been analyzed at 7 day of DR in fly head, gut and fat body. Also the silencing of lncRNA XLOC_076307 resulted in altered expression level of its targets including Gadd45 (involved in FoxO signaling pathway). Together, the results implicated many lncRNAs closely associated with dietary restriction, which could provide a resource for lncRNA in aging and age-related disease field.

Self-Assembled Tetrahedral DNA Nanostructures Promote Adipose-Derived Stem Cell Migration via lncRNA XLOC 010623 and RHOA/ROCK2 Signal Pathway.

Self-assembled tetrahedral DNA nanostructures (TDNs) with precise sizes have been extensively applied in various fields owing to their exceptional mechanical rigidity, structural stability, and modification versatility. In addition, TDNs can be internalized by mammalian cells and remain mainly intact within the cytoplasm by escaping degradation by nucleases. Here, we studied the effects of TDNs on cell migration and the underlying molecular mechanisms. TDNs remarkably enhanced the migration of rat adipose-derived stem cells and down-regulated the long noncoding RNA (lncRNA) XLOC 010623 to activate the mRNA expression of Tiam1 and Rac1. Furthermore, TDNs highly up-regulated the mRNA and protein expression of RHOA, ROCK2, and VCL. These results indicate that TDNs suppressed the transcription of lncRNA XLOC 010623 and activated the TIAM1/RAC1 and RHOA/ROCK2 signaling pathways to promote cell migration. On the basis of these findings, TDNs show a high potential for application in tissue repair and regenerative medicine as a functional three-dimensional DNA nanomaterial.

Transcriptome Analysis Reveals Distinct Gene Expression Profiles in Eosinophilic and Noneosinophilic Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP), one of the most prevalent chronic diseases, is characterized by persistent inflammation of sinonasal mucosa. However, the pathogenesis of CRSwNP remains unclear. Here, we performed next-generation RNA sequencing and a comprehensive bioinformatics analyses to characterize the transcriptome profiles, including mRNAs and long noncoding RNAs (lncRNAs), in patients with eosinophilic and noneosinophilic CRSwNP. A total of 1917 novel lncRNAs and 280 known lncRNAs were identified. We showed eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (non-ECRSwNP) display distinct transcriptome profiles. We identified crucial pathways, including inflammatory, immune response and extracellular microenvironment, connected to the pathogenetic mechanism of CRSwNP. We also discovered key lncRNAs differentially expressed, including lncRNA XLOC_010280, which regulates CCL18 and eosinophilic inflammation. The qRT-PCR and in situ RNA hybridization results verified the key differentially expressed genes. The feature of distinct transcriptomes between ECRSwNP and non-ECRSwNP suggests the necessity to develop specific biomarkers and personalized therapeutic strategies. Our findings lay a solid foundation for subsequent functional studies of mRNAs and lncRNAs as diagnostic and therapeutic targets in CRSwNP by providing a candidate reservoir.

Low expression of long noncoding XLOC_010588 indicates a poor prognosis and promotes proliferation through upregulation of c-Myc in cervical cancer

ObjectiveThe identification and investigation of cancer-associated long non-coding RNAs are important for understanding the molecular biology of cancer. The aim of the present study was to examine the expression pattern of lncRNA XLOC_010588 in cervical cancer and to evaluate its biological role and clinical significance in tumor progression. MethodsWe examined the expression of XLOC_010588 in 218 cervical cancer tissues and matched 218 adjacent normal tissues using real-time qRT-PCR. Over-expression and RNA interference approaches were used to investigate the biological functions of XLOC_010588. The effect of XLOC_010588 on proliferation was evaluated by MTT and BrdU assays. Western blot assays were used to investigate the molecular mechanism by which XLOC_010588 increases cervical cancer cell proliferation. ResultsThe results showed that XLOC_010588 expression in cervical cancer was significantly downregulated. Decreased XLOC_010588 expression was correlated with FIGO stage, tumor size and SCC-Ag. Moreover, cervical cancer patients with XLOC_010588 lower expression have shown poorer prognosis. Multivariate Cox regression analyses showed that XLOC_010588 expression served as an independent predictor for overall survival. Ectopic expression of XLOC_010588 inhibited the proliferation of HeLa and SiHa cells. By contrast, knockdown of XLOC_010588 promoted the growth of HCC94 cells. Western blot assays confirmed that XLOC_010588 physically associates with c-Myc, consequently decreasing the expression of c-Myc. The expression of XLOC_010588 and c-Myc is strongly correlated in cervical cancer tissues. ConclusionThese results suggested that XLOC_010588 plays a pivotal role in cervical cancer cell proliferation via decreasing c-Myc expression and implicated the potential application of XLOC_010588 in cervical cancer therapy.