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Genome-wide identification and characterization of long intergenic noncoding RNAs in the regenerative flatworm Macrostomum lignano

Azlan A, Halim MA, Azzam G

Genomics, 2020 03;112(2):1273-1281.
PMID: 31381967 DOI: 10.1016/j.ygeno.2019.07.016

The free-living flatworm Macrostoma lignano (M. lignano) is an emerging model organism for aging and regeneration research. Long intergenic non-coding RNAs (lincRNAs) have important roles in many biological processes such as aging, stem cell maintenance and differentiation. However, to date, there is no systematic identification of lincRNAs in M. lignano. By using public RNA-seq data, we identified a total of 2547 lincRNA transcripts in M. lignano genome. We discovered that M. lignano lincRNAs shared many characteristics with other species such as shorter in length, lower GC content, and lower in expression compared to protein-coding genes. Unlike protein-coding genes, M. lignano lincRNAs showed higher tendency to be expressed in temporal and region-specific fashion. Additionally, co-expression network analysis and functional enrichment suggest that M. lignano lincRNAs have potential roles in regeneration. This study will provide important resources and pave the way for investigations on non-coding genes involved in aging and regeneration.

Matched MeSH terms: RNA, Long Noncoding/metabolism
Fulltext Systematic identification and characterization of Aedes aegypti long noncoding RNAs (lncRNAs)

Azlan A, Obeidat SM, Yunus MA, Azzam G

Sci Rep, 2019 08 21;9(1):12147.
PMID: 31434910 DOI: 10.1038/s41598-019-47506-9

Long noncoding RNAs (lncRNAs) play diverse roles in biological processes. Aedes aegypti (Ae. aegypti), a blood-sucking mosquito, is the principal vector responsible for replication and transmission of arboviruses including dengue, Zika, and Chikungunya virus. Systematic identification and developmental characterisation of Ae. aegypti lncRNAs are still limited. We performed genome-wide identification of lncRNAs, followed by developmental profiling of lncRNA in Ae. aegypti. We identified a total of 4,689 novel lncRNA transcripts, of which 2,064, 2,076, and 549 were intergenic, intronic, and antisense respectively. Ae. aegypti lncRNAs share many characteristics with other species including low expression, low GC content, short in length, and low conservation. Besides, the expression of Ae. aegypti lncRNAs tend to be correlated with neighbouring and antisense protein-coding genes. A subset of lncRNAs shows evidence of maternal inheritance; hence, suggesting potential role of lncRNAs in early-stage embryos. Additionally, lncRNAs show higher tendency to be expressed in developmental and temporal specific manner. The results from this study provide foundation for future investigation on the function of Ae. aegypti lncRNAs.

Matched MeSH terms: RNA, Long Noncoding/metabolism*
Long noncoding RNAs as biotargets in cisplatin-based drug resistance

Abu N, Hon KW, Jeyaraman S, Jamal R

Future Oncol, 2018 Dec;14(29):3085-3095.
PMID: 30468082 DOI: 10.2217/fon-2018-0303

Since its discovery, cisplatin has become the key drug in chemotherapy for cancers. Nevertheless, chemoresistance in cancers has become an impediment in using cisplatin for cancer treatment. The resistance toward cisplatin is multifaceted as it involves multiple cellular pathways. Ever since the knowledge of long noncoding RNAs as modulators of various molecular pathways came to light, the interest in the biological function of lncRNAs as biomarkers has increased dramatically. Numerous studies have reported the link between the dysregulation of lncRNAs and drug resistance in cancers. More importantly, several lncRNAs were found to be vital in regulating cisplatin resistance. Therefore, this review summarizes the recent efforts in linking between cisplatin resistance and different types of lncRNAs.

Matched MeSH terms: RNA, Long Noncoding/metabolism*
Toward a Reference Gene Catalog of Human Primary Monocytes

Mirsafian H, Ripen AM, Manaharan T, Mohamad SB, Merican AF

OMICS, 2016 11;20(11):627-634.
PMID: 27828772

Transcriptome analyses based on high-throughput RNA sequencing (RNA-Seq) provide powerful and quantitative characterization of cell types and in-depth understanding of biological systems in health and disease. In this study, we present a comprehensive transcriptome profile of human primary monocytes, a crucial component of the innate immune system. We performed deep RNA-Seq of monocytes from six healthy subjects and integrated our data with 10 other publicly available RNA-Seq datasets of human monocytes. A total of 1.9 billion reads were generated, which allowed us to capture most of the genes transcribed in human monocytes, including 11,994 protein-coding genes, 5558 noncoding genes (including long noncoding RNAs, precursor miRNAs, and others), 2819 pseudogenes, and 7034 putative novel transcripts. In addition, we profiled the expression pattern of 1155 transcription factors (TFs) in human monocytes, which are the main molecules in controlling the gene transcription. An interaction network was constructed among the top expressed TFs and their targeted genes, which revealed the potential key regulatory genes in biological function of human monocytes. The gene catalog of human primary monocytes provided in this study offers significant promise and future potential clinical applications in the fields of precision medicine, systems diagnostics, immunogenomics, and the development of innovative biomarkers and therapeutic monitoring strategies.

Matched MeSH terms: RNA, Long Noncoding/metabolism
Fulltext Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

Li HB, You QS, Xu LX, Sun LX, Abdul Majid AS, Xia XB, et al.

Cell Physiol Biochem, 2017;43(5):2117-2132.
PMID: 29065394 DOI: 10.1159/000484231

BACKGROUND/AIMS: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma.
METHODS: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis.
RESULTS: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups.
CONCLUSION: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

Matched MeSH terms: RNA, Long Noncoding/metabolism*