Systematic Analysis of Long Noncoding RNAs in the Senescence-accelerated Mouse Prone 8 Brain Using RNA Sequencing

Zhang, Shuai; Qin, Chunxia; Cao, Guoqiong; Xin, Wenfeng; Cheng, Feng; Zhang, Wensheng

doi:10.1038/mtna.2016.57

Cited by 41 publications

(45 citation statements)

References 49 publications

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“…Recently, accumulating data demonstrated that non-coding RNAs (ncRNAs) are key regulators in both normal physiological and pathological conditions [5][6][7]. LncRNAs which are defined as those longer than~200 nucleotides, have been extensively characterized and it is evident that they are taking crucial roles in pathologies, including cancers [8][9][10][11][12][13]. In our previous study (GEO, http://www.ncbi.nlm.nih.…”

Section: Introductionmentioning

confidence: 99%

Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

Zhao

Liu

et al. 2017

J Cellular Molecular Medi

122

126

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non‐coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC. Linc00511 levels in PDAC tissue specimens and cell lines were examined by quantitative real‐time PCR. Corresponding adjacent non‐neoplastic tissues were used as controls. The function of linc00511 in PDAC cell lines was determined by RNA interference approach in vitro and in vivo. Fluorescence in situ hybridization (FISH) was used to characterize linc00511 expression in PDAC cells. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were obtained from bioinformatic analysis, luciferase assays and RIP assays. The association between the linc00511/hsa‐miR29b‐3p axis and VEGFA was verified by Western blotting assay. Immunohistochemistry was performed to evaluate the expression of VEGFA in PDAC samples. The aberrant up‐regulation of linc00511 was detected in PDAC cell lines and patient specimens compared with controls. An increase in linc00511 expression indicates the adverse clinical pathological characteristics and poor prognosis. Functionally, linc00511 depletion in PDAC cells decreased proliferation, migration, invasion and endothelial tube formation. Mechanistically, linc00511 could up‐regulate VEGFA via its competing endogenous RNA (ceRNA) activity on hsa‐miR‐29b‐3p. In summary, our results define an important axis controlling proliferation, invasion and tumour angiogenesis in PDAC. Linc00511 is a novel lncRNA that plays a significant regulatory role in the pathogenesis and progression of PDAC. Thus, Linc00511 represents a new prognostic biomarker to predict clinical outcome of PDAC patients after surgery and may serve as a potential therapeutic target for PDAC treatment.

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Section: Introductionmentioning

confidence: 99%

Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

Zhao

Liu

et al. 2017

J Cellular Molecular Medi

122

126

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“…5 Long noncoding RNAs (lncRNAs) are a major class of ncRNAs with over 200 nucleotides in length. 6 In recent years, emerging evidence has indicated that lncRNAs can play important roles in cellular and biological functions. They participate in cancer development post-transcriptionally or modulate genes through chromatin regulation.…”

mentioning

confidence: 99%

Long noncoding RNA LINC00961 inhibits cell proliferation and induces cell apoptosis in human non–small cell lung cancer

Huang

Lei

Tan

et al. 2018

J of Cellular Biochemistry

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Long noncoding RNAs (LncRNAs) have been identified in multiple human cancer types, including lung cancer. An increasing number of studies have indicated that lncRNAs can function as important gene regulators. However, the biological mechanism of LINC00961 in lung cancerremains poorly understood. In our current study, we recognized lncRNA LINC00961, and we observed that it was significantly reduced in human non-small cell lung cancer (NSCLC) tissues. LINC00961 was elevated by infecting LV-LINC00961, while decreased by LV-shLINC00961 in H226 and A549 cells. Furthermore, it was shown that LINC00961 overexpression greatly inhibited lung cancer cell proliferation, whereas downregulated LINC00961 induced cell proliferation. In addition, further experiments showed that restoration of LINC00961 could dramatically increase apoptotic ratios of NSCLC H226 and A549 cells, and knockdown of LINC00961 exhibited an opposite effect. Moreover, Western blot analysis showed that upregulation of LINC00961 repressed proliferating cell nuclear antigen expression and increased Bax expression, indicating that it acts as an important pro-apoptosis gene. Conversely, inhibition of LINC00961 induced proliferating cell nuclear antigen expression and restrained Bax protein levels. Taking these together, LINC00961 might play a tumor suppressive role in NSCLC progression, and it could serve as a novel prognostic biomarker in NSCLC diagnosis and treatment.

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“…Recent studies have shifted focus to dysregulated gene alterations and regulations in brain aging and related diseases, particularly AD and PD. We have conducted considerable work previously on this aspect, including lncRNA, miRNA, circRNA, and DNA methylation (Zhang et al 2016;. The anomaly of tRFs may exert a great influence on brain aging and related diseases.…”

Section: Discussionmentioning

confidence: 99%

“…In this research, the expression levels of the tRFs and mRNAs showed significant difference between the SAMP8 and SAMR1 mice and were hence analyzed. Our previous study (Zhang et al 2016) revealed that 482 mRNA transcripts were differentially expressed between SAMP8 and SAMR1 mouse brains at 7 months of age (adjusted p value < 0.05, Supplementary Table S4).…”

Section: Target Predictionmentioning

confidence: 99%

“…The senescence-accelerated mouse resistant 1 (SAMR1) strain undergoes a normal aging process and is often used as the reference group . In our previous studies, we analyzed the changes of lncRNA, circRNA, miRNA, and DNA methylation in the brain of SAMP8, and the related mechanisms for regulating gene expression (Zhang et al 2016;. Are there any changes of tRFs in SAMP8 mouse brain?…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide identification of functional tRNA-derived fragments in Senescence-accelerated mouse prone 8 brain

Zhang

Zheng

et al. 2018

Preprint

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AbstracttRNA-derived fragments (tRFs) have been linked previously to the development of various diseases, such as cancer and viral infection. However, tRFs seem also related to brain aging and related diseases, especially Alzheimer and Parkinson disease. RNA sequencing, a state-of-the-art technology, has allowed for investigation of tRFs in this field. In this study, we investigated the changes of tRFs in the brains of a senescence-accelerated mouse model, senescence-accelerated mouse prone 8 (SAMP8), that show age-dependent deficits in learning and memory; and a control model, senescence-accelerated mouse resistant 1 (SAMR1), with normal aging, both at 7 months of age. A total of 570 tRF transcripts were discovered. Among these transcripts, 8, including 3 upregulated and 5 downregulated transcripts, were differentially expressed in the SAMP8 mice. Then, we obtained 110 potential target genes in a miRNA-like pattern. GO survey implicated these target genes in the function of various aspects, e.g. postsynaptic density (GO: 0014069). Furthermore, we assessed in detail those tRFs whose miRNA-like pattern was most likely to affect the progression of either Alzheimer and Parkinson disease, such as AS-tDR-011775 acting on Mobp and Park2. In fact, we found the tRFs to be involved in the regulation of gene expression by means other than the miRNA-like pattern. Therefore, these 8 dysregulated tRFs may hold consequences far into the future and can be attractive biomarkers and valid targets. In brief, our study is the first to provide a comprehensive analysis on tRFs in SAMP8 mouse brain, and this breakthrough identified promising new targets for preventing the age-related changes of brain and the therapeutic intervention of Alzheimer’s and Parkinson’s.

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Systematic Analysis of Long Noncoding RNAs in the Senescence-accelerated Mouse Prone 8 Brain Using RNA Sequencing

Cited by 41 publications

References 49 publications

Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

Long noncoding RNA LINC00961 inhibits cell proliferation and induces cell apoptosis in human non–small cell lung cancer

Genome-wide identification of functional tRNA-derived fragments in Senescence-accelerated mouse prone 8 brain

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