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BC200 (BCYRN1) - The shortest, long, non-coding RNA associated with cancer.

ABSTRACT: With the discovery that the level of RNA synthesis in human cells far exceeds what is required to express protein-coding genes, there has been a concerted scientific effort to identify, catalogue and uncover the biological functions of the non-coding transcriptome. Long, non-coding RNAs (lncRNAs) are a diverse group of RNAs with equally wide-ranging biological roles in the cell. An increasing number of studies have reported alterations in the expression of lncRNAs in various cancers, although unravelling how they contribute specifically to the disease is a bigger challenge. Originally described as a brain-specific, non-coding RNA, BC200 (BCYRN1) is a 200-nucleotide, predominantly cytoplasmic lncRNA that has been linked to neurodegenerative disease and several types of cancer. Here we summarise what is known about BC200, primarily from studies in neuronal systems, before turning to a review of recent work that aims to understand how this lncRNA contributes to cancer initiation, progression and metastasis, along with its possible clinical utility as a biomarker or therapeutic target.

SUBMITTER: Samson J

PROVIDER: S-EPMC6114260 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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BC200 (BCYRN1) - The shortest, long, non-coding RNA associated with cancer.

Samson J J Cronin S S Dean K K

Non-coding RNA research 20180522 3

With the discovery that the level of RNA synthesis in human cells far exceeds what is required to express protein-coding genes, there has been a concerted scientific effort to identify, catalogue and uncover the biological functions of the non-coding transcriptome. Long, non-coding RNAs (lncRNAs) are a diverse group of RNAs with equally wide-ranging biological roles in the cell. An increasing number of studies have reported alterations in the expression of lncRNAs in various cancers, although un ...[more]

PMID: 30175286

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Project description:BackgroundBC200 is a long non-coding RNA expressed at high levels in the brain and elevated in a variety of tumour types. BC200 has a hypothesized role in translational regulation; however, to date the functional role of BC200 in both normal and diseased states remains poorly characterized.MethodsDetailed BC200 expression analyses were performed in tumor cell lines, primary and non-tumorigenic cultured breast and lung cells, and a panel of normal human tissues by quantitative real-time PCR and confirmed by northern blot. Subcellular fractionation was performed to assess BC200 distribution and efficient knock-down of BC200 was established using both locked nucleic acid (LNA) GapmeRs and conventional siRNAs. Cell viability following BC200 knockdown and overexpression was assessed by MTT assay and induction of apoptosis was monitored by Annexin V/PI staining and flow cytometry. Cell cycle arrest and synchronization were performed using serum withdrawal as well as the specific inhibitors Lovastatin, Thymidine, RO3306 and Nocodazole. Synchronization was monitored by fluorescent analysis of cellular DNA content by flow cytometry RESULTS: BC200 expression was substantially upregulated in brain and elevated expression was also observed in testes, small intestine and ovary. Expression in cultured tumour cells was dramatically higher than corresponding normal tissue; however, expression in cultured primary cells was similar to that in immortalized and cancer cell lines. BC200 knockdown resulted in a dramatic loss of viability through growth arrest and induction of apoptosis that could be partially rescued by overexpression of wild-type BC200 but not an siRNA-resistant sequence mutant. A substantial decrease in BC200 expression was observed upon cell confluence or serum deprivation, as well as drug induced cell cycle arrest in G1 or G2 but not S- or M-phases. Upon release from cell cycle arrest, BC200 expression was recovered as cells entered S-phase, but did not follow a periodic expression pattern during synchronized progression through the cell cycle. This elevated expression was critical for the survival of proliferating cancerous and non-cancerous cells, but is dispensable upon senescence or cell cycle arrest.ConclusionsBC200 expression is elevated in proliferating cultured cells regardless of origin. In primary cells, expression is dramatically reduced upon cell cycle arrest by confluence, serum deprivation or chemical inhibition. The lethality of BC200 knockdown is restricted to actively proliferating cells, making it a promising therapeutic target for a broad spectrum of cancers.

Project description:Gastric cancer (GC) is a common type of cancer, and identification of novel diagnostic biomarkers associated with this disease is important. The present study aimed to identify novel diagnostic biomarkers associated with the prognosis of GC, using an integrated bioinformatics approach. Differentially expressed long non-coding RNAs (lncRNAs) associated with GC were identified using Gene Expression Omnibus datasets (GSE58828, GSE72305 and GSE99416) and The Cancer Genome Atlas database. A competing endogenous RNA network that incorporated five lncRNAs [long intergenic non-protein coding RNA 501 (LINC00501), LINC00365, SOX21 antisense divergent transcript 1 (SOX21-AS1), GK intronic transcript 1 (GK-IT1) and DLEU7 antisense RNA 1 (DLEU7-AS1)], 29 microRNAs and 114 mRNAs was constructed. Gene Ontology and protein-protein interaction network analyses revealed that these lncRNAs may be involved in 'biological regulation', 'metabolic process', 'cell communication', 'developmental process', 'cell proliferation', 'reproduction' and the 'cell cycle'. The results of receiver operating characteristic curve analysis demonstrated that LINC00501 (AUC=0.819), LINC00365 (AUC=0.580), SOX21-AS1 (AUC=0.736), GK-IT1 (AUC=0.823) and DLEU7-AS1 (AUC=0.932) had the potential to become valuable diagnostic biomarkers for GC. Associations with clinicopathological characteristics demonstrated that LINC00501 expression was significantly associated with sex (P=0.015) and tumor grade (P=0.022). Furthermore, LINC00365 expression was significantly associated with lymph node metastasis (P=0.025). Gene set enrichment analysis revealed that LINC00501, LINC00365 and SOX21-AS1 were enriched in signaling pathways associated with GC. Reverse transcription-quantitative PCR analysis demonstrated that LINC00501 expression (P=0.043) was significantly upregulated in GC tissues, whereas the expression levels of LINC00365 (P=0.033) and SOX21-AS1 (P=0.037) were significantly downregulated in GC tissues. Taken together, the results of the present study suggest that LINC00501, LINC00365, SOX21-AS1, GK-IT1 and DLEU7-AS1 may be used as novel diagnostic biomarkers for GC, and may be functionally associated with GC development and progression.

Dataset Information

BC200 (BCYRN1) - The shortest, long, non-coding RNA associated with cancer.

Publications

BC200 (BCYRN1) - The shortest, long, non-coding RNA associated with cancer.

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