The Role of cis- and trans-Acting RNA Regulatory Elements in Leukemia

Elcheva, Irina; Spiegelman, Vladimir S.

doi:10.3390/cancers12123854

Cited by 19 publications

(18 citation statements)

References 211 publications

(256 reference statements)

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“…As a type of non-coding RNA, LncRNA can regulate gene expression at multiple levels, including transcriptional and post-transcriptional regulation, translation, and post-translational modification, and thus affect a variety of biological functions, such as cell proliferation, differentiation, and apoptosis in cancer [ 10 ]. Among them, cis-acting is an important regulatory function of lncRNA, and its knockdown or overexpression will lead to changes in the expression of adjacent genes on the chromosome [ 11 ]. At present, relevant studies have shown that some lncRNAs are overexpressed, under-expressed, or even not expressed in AML.…”

Section: Introductionmentioning

confidence: 99%

“…At present, relevant studies have shown that some lncRNAs are overexpressed, under-expressed, or even not expressed in AML. Their abnormal expression will cis-regulate the expression of neighboring genes, and then play a role in promoting or suppressing cancer [ 11 , 12 ]. For example, Fernando et al found that a novel lncRNA CASC15 was up-regulated in acute lymphoblastic leukemia (B-ALL), and subsequently affected cell survival and proliferation by driving the expression of its adjacent gene SOX4 on the chromosome through the cis mechanism, thereby delaying the progression of acute leukemia [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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LncRNA USP30-AS1 promotes the survival of acute myeloid leukemia cells by cis-regulating USP30 and ANKRD13A

Wei

Deng

et al. 2021

Human Cell

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Acute myeloid leukemia (AML) is a malignant tumor derived from leukemia stem cells, with complicated pathogenesis. LncRNAs play an important role in tumors genesis and progression. According to results from bioinformatics analysis, lncRNA USP30-AS1 is highly expressed in AML and both the high expression of USP30-AS1 and low methylation level at Cg03124318 locus of USP30-AS1 gene promoter are associated with poor prognosis of AML. This study knocked down and overexpressed USP30-AS1 to determine the roles in AML cell lines. High-throughput sequencing was performed to explore the genes regulated by USP30-AS1. Results showed that USP30-AS1 promoted AML cell viability and inhibited apoptosis. Genes regulated by USP30-AS1 are mainly related to genetic regulation and immune system. Among them, USP30 and ANKRD13A genes are close to USP30-AS1 gene in chromosome. Knockdown of USP30, but not ANKRD13A, abolished the cancer-promoting effects of USP30-AS1. ANKRD13A recognizes Lys-63-linked polyubiquitin chain in HLA-I. USP30-AS1 induced HLA-I internalization from the cell membrane by up-regulating ANKRD13A, which might induce the immune escape of AML cells. ChIP analysis revealed that the regulatory effects of USP30-AS1 on USP30 and ANKRD13A are associated with H3K4me3 and H3K27Ac. In summary, USP30-AS1 probably promotes AML cell survival by cis-regulating USP30 and ANKRD13A.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LncRNA USP30-AS1 promotes the survival of acute myeloid leukemia cells by cis-regulating USP30 and ANKRD13A

Wei

Deng

et al. 2021

Human Cell

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“…DElncRNAs, which constituted 181 cis lncRNA-gene pairs. The cis-regulation function of non-coding RNA might participate in various biological processes (21) while the cis-regulation function of lncRNA might affect tumor progression (22,23). Our analysis indicated that DElncRNAs were mainly positive with adjacent protein-coding genes, with a negative correlation being relatively few in number.…”

Section: Discussionmentioning

confidence: 74%

Pepsinogen C expression–related lncRNA/circRNA/mRNA profile and its co-mediated ceRNA network in gastric cancer

Yan

Ding

Shen

et al. 2021

Funct Integr Genomics

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BackgroundThe expression of pepsinogen C (PGC) is considered an ideal negative biomarker of gastric cancer, but its pathological mechanisms remain unclear. This study aims to analyze competing endogenous RNA (ceRNA) networks related to PGC expression at a posttranscriptional level and build an experimental basis for studying the role of PGC in the progression of gastric cancer. Materials and methodsRNA sequencing technology was used to detect the differential expression pro les of PGC-related long non-coding (lnc)RNAs, circular (circ)RNAs, and mRNAs. The online database, STRING, was used to construct protein-protein interaction (PPI) networks of differentially expressed (DE) mRNAs. A ggcorrplot R package and online database were used to construct DElncRNAs/DEcircRNAs co-mediated PGC expression-related ceRNA networks. In vivo and in vitro validations were performed using quantitative reverse transcription-PCR. ResultsRNA sequencing found 637 DEmRNAs, 698 DElncRNAs, and 38 DEcircRNAs. The PPI network of PGC expression-related mRNAs consisted of 503 nodes and 1179 edges. CFH, PPARG, and MUC6 directly interacted with PGC. Enrichment analysis suggested that DEmRNAs were mainly enriched in cancer-related pathways. Eleven DElncRNAs, 13 circRNAs, and 35 miRNA-mRNA pairs were used to construct ceRNA networks co-mediated by DElncRNAs and DEcircRNAs that were PGC expression-related. The network directly related to PGC was as follows: SNHG16/hsa_circ_0008197-hsa-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p-PGC. Quantitative reverse transcriptase PCR validation results showed that PGC, PPARG, SNHG16, and hsa_circ_0008197 were differentially expressed in gastric cancer cells and

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“…It is well established that lncRNAs can exert regulatory effects on mRNAs ( Quinn and Chang, 2016 ; Tan-Wong et al, 2019 ; Elcheva and Spiegelman, 2020 ). The target genes of lncRNAs can be predicted on the basis of either their physical positions, in the case of antisense and cis- regulatory mechanisms, or their coexpression relationships, in the case of trans -regulation.…”

Section: Discussionmentioning

confidence: 99%

Integrated lncRNA and mRNA Transcriptome Analyses in the Ovary of Cynoglossus semilaevis Reveal Genes and Pathways Potentially Involved in Reproduction

et al. 2021

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Long non-coding RNAs (lncRNAs) have been reported to be involved in multiple biological processes. However, the roles of lncRNAs in the reproduction of half-smooth tongue sole (Cynoglossus semilaevis) are unclear, especially in the molecular regulatory mechanism driving ovarian development and ovulation. Thus, to explore the mRNA and lncRNA mechanisms regulating reproduction, we collected tongue sole ovaries in three stages for RNA sequencing. In stage IV vs. V, we identified 312 differentially expressed (DE) mRNAs and 58 DE lncRNAs. In stage V vs. VI, we identified 1,059 DE mRNAs and 187 DE lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DE mRNAs were enriched in ECM-receptor interaction, oocyte meiosis and steroid hormone biosynthesis pathways. Furthermore, we carried out gene set enrichment analysis (GSEA) to identify potential reproduction related-pathways additionally, such as fatty metabolism and retinol metabolism. Based on enrichment analysis, DE mRNAs with a potential role in reproduction were selected and classified into six categories, including signal transduction, cell growth and death, immune response, metabolism, transport and catabolism, and cell junction. The interactions of DE lncRNAs and mRNAs were predicted according to antisense, cis-, and trans-regulatory mechanisms. We constructed a competing endogenous RNA (ceRNA) network. Several lncRNAs were predicted to regulate genes related to reproduction including cyp17a1, cyp19a1, mmp14, pgr, and hsd17b1. The functional enrichment analysis of these target genes of lncRNAs revealed that they were involved in several signaling pathways, such as the TGF-beta, Wnt signaling, and MAPK signaling pathways and reproduction related-pathways such as the progesterone-mediated oocyte maturation, oocyte meiosis, and GnRH signaling pathway. RT-qPCR analysis showed that two lncRNAs (XR_522278.2 and XR_522171.2) were mainly expressed in the ovary. Dual-fluorescence in situ hybridization experiments showed that both XR_522278.2 and XR_522171.2 colocalized with their target genes cyp17a1 and cyp19a1, respectively, in the follicular cell layer. The results further demonstrated that lncRNAs might be involved in the biological processes by modulating gene expression. Taken together, this study provides lncRNA profiles in the ovary of tongue sole and further insight into the role of lncRNA involvement in regulating reproduction in tongue sole.

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The Role of cis- and trans-Acting RNA Regulatory Elements in Leukemia

Cited by 19 publications

References 211 publications

LncRNA USP30-AS1 promotes the survival of acute myeloid leukemia cells by cis-regulating USP30 and ANKRD13A

LncRNA USP30-AS1 promotes the survival of acute myeloid leukemia cells by cis-regulating USP30 and ANKRD13A

Pepsinogen C expression–related lncRNA/circRNA/mRNA profile and its co-mediated ceRNA network in gastric cancer

Integrated lncRNA and mRNA Transcriptome Analyses in the Ovary of Cynoglossus semilaevis Reveal Genes and Pathways Potentially Involved in Reproduction

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