The lncRNA SLCO4A1‐AS1/miR‐876‐3p/RBBP6 axis regulates cell proliferation and apoptosis in acute lymphocytic leukemia via the JNK signaling pathway

Mao, Jianping; Gao, Wen; Xue, Lijun; Wang, Juan; Zhao, Liang

doi:10.1111/ijlh.13501

Cited by 8 publications

(3 citation statements)

References 37 publications

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“…A recent study reported that lncRNA Slco4a1 could promote the growth and invasion of bladder cancer by sponging miR-335-5p (17). LncRNA Slco4a1 knockdown could regulate cell proliferation and apoptosis via the JNK signaling pathway (24). In this study, we observed that lncRNA Slco4a1 could positively regulate the post-transcriptional expression of POU5F1 through miR-335-5p.…”

Section: Discussionsupporting

confidence: 49%

Kawasaki disease: lncRNA Slco4a1 regulates the progression of human umbilical vein endothelial cells by targeting the miR-335-5p/POU5F1 axis

Hao¹,

Zhang²,

Pan³

et al. 2022

Transl Pediatr

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Background: Kawasaki disease (KD) is an autoimmune disease with systemic vasculitis as the main pathological change, and is most common in children under 5. The role of long non-coding RNAs (lncRNAs) in human diseases has been highlighted. LncRNA Slco4a1 was reported to promote cell growth and act as an oncogenic regulator in cancer. However, the role of lncRNA Slco4a1 in KD remains unclear. This study aimed to investigate the role and mechanism of lncRNA Slco4a1 in KD.Methods: Enzyme linked immunosorbent assay (ELISA), qRT-PCR, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining were conducted to explore the function of lncRNA Slco4a1. The interaction between POU5F1 and miR-335-5p was analyzed by the RIP assay and dual luciferase assay.Results: LncRNA Slco4a1 was significantly upregulated in the serum of KD patients compared with healthy controls. LncRNA Slco4a1 was upregulated in human umbilical vein endothelial cells (HUVECs) stimulated with KD serum. LncRNA Slco4a1 overexpression could promote the expression of inflammatory factors and apoptosis in HUVECs. The number of inflammatory cells and the infiltration area of the coronary artery in KD rats were decreased after lncRNA Slco4a1 silencing. Furthermore, lncRNA Slco4a1 is a sponge of miR-335-5p and negatively regulated the expression of miR-335-5p. POU5F1 was the downstream target of miR-335-5p, and miR-335-5p overexpression could upregulate the expression of POU5F1. Additionally, miR-335-5p overexpression could inhibit the expression of inflammatory factors and apoptosis in HUVECs. We further investigated the effect of lncRNA Slco4a1 on the mitogen-activated protein kinase (MAPK) signaling pathway, and the results showed that lncRNA Slco4a1 could promote the activation of the MAPK signaling pathway.Conclusions: Together, these results indicated that lncRNA Slco4a1 could regulate the progression of HUVECs in KD by targeting the miR-335-5p/POU5F1 axis, providing new insights for KD treatment.

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Section: Discussionsupporting

confidence: 49%

Kawasaki disease: lncRNA Slco4a1 regulates the progression of human umbilical vein endothelial cells by targeting the miR-335-5p/POU5F1 axis

Hao¹,

Zhang²,

Pan³

et al. 2022

Transl Pediatr

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“…In this study, we further showed that SLCO4A1-AS1 promotes CRC proliferation and cell cycle progression in vitro, and tumourigenesis in vivo. To date, SLCO4A1-AS1-related mechanistic investigations have focused on miRNAs, and some papers have revealed that SLCO4A1-AS1 functions as a competing endogenous RNA (ceRNA) to inhibit the activities of several miRNAs, including miR-223-3p [ 18 ], miR-150-3p [ 17 ], miR-4701-5p [ 16 ], miR-335-5p [ 33 ], miR-876-3p [ 37 ], and miR-508-3p [ 19 ]. Notably, in addition to miR-223-3p, the abundance of other miRNAs is very low in CRC tissues (data not shown), suggesting that these miRNAs are not key molecules mediating the tumour-promoting functions of SLCO4A1-AS1 under physiological and pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling

et al. 2022

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Background SLCO4A1-AS1 was found to be upregulated in several cancer types, including colorectal cancer (CRC). However, the detailed roles of SLCO4A1-AS1 in CRC remain to be elucidated. Therefore, we investigated the functions, mechanism, and clinical significance of SLCO4A1-AS1 in colorectal tumourigenesis. Methods We measured the expression of SLCO4A1-AS1 in CRC tissues using qRT-PCR and determined its correlation with patient prognosis. Promoter methylation analyses were used to assess the methylation status of SLCO4A1-AS1. Gain- and loss-of-function assays were used to evaluate the effects of SLCO4A1-AS1 on CRC growth in vitro and in vivo. RNA pull-down, RNA immunoprecipitation, RNA-seq, luciferase reporter and immunohistochemistry assays were performed to identify the molecular mechanism of SLCO4A1-AS1 in CRC. Results SLCO4A1-AS1 was frequently upregulated in CRC tissues based on multiple CRC cohorts and was associated with poor prognoses. Aberrant overexpression of SLCO4A1-AS1 in CRC is partly attributed to the DNA hypomethylation of its promoter. Ectopic SLCO4A1-AS1 expression promoted CRC cell growth, whereas SLCO4A1-AS1 knockdown repressed CRC proliferation both in vitro and in vivo. Mechanistic investigations revealed that SLCO4A1-AS1 functions as a molecular scaffold to strengthen the interaction between Hsp90 and Cdk2, promoting the protein stability of Cdk2. The SLCO4A1-AS1-induced increase in Cdk2 levels activates the c-Myc signalling pathway by promoting the phosphorylation of c-Myc at Ser62, resulting in increased tumour growth. Conclusions Our data demonstrate that SLCO4A1-AS1 acts as an oncogene in CRC by regulating the Hsp90/Cdk2/c-Myc axis, supporting SLCO4A1-AS1 as a potential therapeutic target and prognostic factor for CRC.

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“…We found that the DGUOK-AS1 antisense RNA targets several immune-relevant microRNAs—in addition to the DGUOK transcript itself. DGUOK-AS1 targets miR-1-3p (which facilitates Th17 differentiation [ 45 ]), miR-138-5p (which promotes TNFα-induced apoptosis through PTEN/PI3K/Akt signaling [ 46 ]), miR-148a-3p and miR-148b-3p (the primary biomarker for lupus nephritis [ 47 ] and a potent PTEN activator), miR-151a-3p (another biomarker of lupus nephritis [ 48 ]), miR-653-5p (an miRNA active in Behçet’s syndrome inflammation [ 49 ]), and miR-876-3p (which modulates proliferation and apoptosis in lymphocytic leukemia through JNK signaling [ 50 ]). A separate search for non-miRNA genes targeted by DGUOK-AS1 revealed bradykinin—a key inflammatory mediator—and the lncRNA Xist , the primary determinant of X-inactivation and autoimmune sex bias.…”

Section: Discussionmentioning

confidence: 99%

Discovery and Functional Characterization of Two Regulatory Variants Underlying Lupus Susceptibility at 2p13.1

Fazel-Najafabadi

Rallabandi

Singh

et al. 2022

Genes

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Genome-wide association studies have identified 2p13.1 as a prominent susceptibility locus for systemic lupus erythematosus (SLE)—a complex, multisystem autoimmune disease. However, the identity of underlying causal variant (s) and molecular mechanisms for increasing disease susceptibility are poorly understood. Using meta-analysis (cases = 10,252, controls = 21,604) followed by conditional analysis, bioinformatic annotation, and eQTL and 3D-chromatin interaction analyses, we computationally prioritized potential functional variants and subsequently experimentally validated their effects. Ethnicity-specific meta-analysis revealed striking allele frequency differences between Asian and European ancestries, but with similar odds ratios. We identified 20 genome-wide significant (p < 5 × 10−8) variants, and conditional analysis pinpointed two potential functional variants, rs6705628 and rs2272165, likely to explain the association. The two SNPs are near DGUOK, mitochondrial deoxyguanosine kinase, and its associated antisense RNA DGUOK-AS1. Using luciferase reporter gene assays, we found significant cell type- and allele-specific promoter activity at rs6705628 and enhancer activity at rs2272165. This is supported by ChIP-qPCR showing allele-specific binding with three histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), transcriptional coactivator p300, CCCTC-binding factor (CTCF), and transcription factor ARID3A. Transcriptome data across 28 immune cell types from Asians showed both SNPs are cell-type-specific but only in B-cells. Splicing QTLs showed strong regulation of DGUOK-AS1. Genotype-specific DGOUK protein levels are supported by Western blots. Promoter capture Hi-C data revealed long-range chromatin interactions between rs2272165 and several nearby promoters, including DGUOK. Taken together, we provide mechanistic insights into how two noncoding variants underlie SLE risk at the 2p13.1 locus.

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The lncRNA SLCO4A1‐AS1/miR‐876‐3p/RBBP6 axis regulates cell proliferation and apoptosis in acute lymphocytic leukemia via the JNK signaling pathway

Cited by 8 publications

References 37 publications

Kawasaki disease: lncRNA Slco4a1 regulates the progression of human umbilical vein endothelial cells by targeting the miR-335-5p/POU5F1 axis

Kawasaki disease: lncRNA Slco4a1 regulates the progression of human umbilical vein endothelial cells by targeting the miR-335-5p/POU5F1 axis

SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling

Discovery and Functional Characterization of Two Regulatory Variants Underlying Lupus Susceptibility at 2p13.1

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