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Downregulation of lncRNA XR_429159.1 could promote brain metastasis in patients with limited-stage small-cell lung cancer

ABSTRACT: Purpose: To identify the aberrant long non-coding RNA (lncRNA) and explore the predictive value of lncRNA on the risk of brain metastases (BMs) for patients with limited-stage small cell lung cancer (SCLC). Patients and Methods: We executed an array of lncRNA and mRNA chip assays on peripheral blood mononuclear cells of SCLC patients with BM comparing to others without BMs to identify the lncRNAs relating to BMs. Then validation was conducted in clinical data to confirm the relationship of lncRNAs and BMs furtherly. We estimated the cumulative incidence of BMs using the Kaplan-Meier method and differences between the groups were analyzed using the log-rank test. Results: The expression of 67 lncRNAs (27 up, 40 down) and 47 mRNAs (20 up, 27 down) were different significantly in BM groups comparing to the group without BMs (fold change ≥ 2.0, p value ≤0.05) which were found by lncRNA and mRNA chip assays initially. Four lncRNAs were verified by qRT-PCR to confirm the accuracy of the microarray data and then the results of 11 pairs of patients (11 patients with BMs, while 11 patients without BMs) showed that low expression of LncRNA XR_429159.1 was the high-risk factor of BM. Further clinical data showed that the BM incidence of 25 patients with low level LncRNA XR_429159.1 was 31% at 1-year, and that was 14.3% in the 18 patients with high level LncRNA XR_429159.1, p = 0.035. Conclusion: Our present study identified that low expression of lncRNA XR_429159.1 was the high-risk factor of BM in patients with limited-stage SCLC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161968 | GEO | 2021/04/16

REPOSITORIES: GEO

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Project description:Only a minuscule fraction of long non-coding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but comparative analyses have been precluded by our ignorance of lncRNAs in non-model organisms. Here, we use RNA sequencing to identify lncRNAs in eleven tetrapod species and we present the first large-scale evolutionary study of lncRNA repertoires and expression patterns. We identify ~11,000 primate- specific lncRNA families, which show evidence for selective constraint during recent evolution, and ~2,400 highly conserved lncRNAs (including ~400 genes that likely originated more than 300 million years ago). We find that lncRNAs, in particular ancient ones, are generally actively regulated and may predominantly function in embryonic development. lncRNA X-inactivation patterns reveal an extremely female-biased monotreme-specific lncRNA, which may partially compensate X-dosage in this lineage. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but global patterns like tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network, which surprisingly contains many lncRNA hubs, suggests potential functions for lncRNAs in fundamental processes like spermatogenesis or synaptic transmission, but also in more specific mechanisms such as placenta growth suppression through miRNA production. [Batch 1 and 2] To broaden our understanding of lncRNA evolution, we used an extensive RNA-seq dataset to establish lncRNA repertoires and homologous gene families in 11 tetrapod species. We analyzed the poly- adenylated transcriptomes of 8 organs (cortex/whole brain without cerebellum, cerebellum, heart, kidney, liver, placenta, ovary and testis) and 11 species (human, chimpanzee, bonobo, gorilla, orangutan, macaque, mouse, opossum, platypus, chicken and the frog Xenopus tropicalis), which shared a common ancestor ~370 millions of years (MY) ago. Our dataset included 47 strand-specific samples, which allowed us to confirm the orientation of gene predictions and to address the evolution of sense-antisense transcripts. See also GSE43721 (Soumillon et al, Cell Reports, 2013) for three strand-specific samples for mouse brain, liver and testis.

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Downregulation of lncRNA XR_429159.1 could promote brain metastasis in patients with limited-stage small-cell lung cancer

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