MIR503HG: A potential diagnostic and therapeutic target in human diseases

Han, Xue; Li, Bo; Zhang, Shitai

doi:10.1016/j.biopha.2023.114314

Cited by 7 publications

(7 citation statements)

References 149 publications

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“…We predicted their lower expression in resistant cells based on increased expression of DEL MIR503HG in TAMR-LTEDI cells. MIR503HG is known to sponge the interfering miRNAs allowing PI3K-mTOR activation and subsequent ETR (42). Moreover, miR424 arises from MIR503HG and its reduced expression as predicted by our network allows increased expression of VEGF that participates in neo-angiogenesis of tumors (42,43).…”

Section: Discussionmentioning

confidence: 99%

“…MIR503HG is known to sponge the interfering miRNAs allowing PI3K-mTOR activation and subsequent ETR (42). Moreover, miR424 arises from MIR503HG and its reduced expression as predicted by our network allows increased expression of VEGF that participates in neo-angiogenesis of tumors (42,43). FLT4 is the receptor for VEGF and it is one of the 7 ceRNA network genes that displayed high expression in resistant cells.…”

Section: Discussionmentioning

confidence: 99%

“…Vilquin et al have shown that depletion of miR-424 and upregulation of miR-205 resulted in Aromatase Inhibitor resistance phenotype in ER+ cells (35). miR-497-5p and miR-195 interfere with PI3K-mTOR signalling and MIR503HG is known to sponge the interfering miRNAs to promote subsequent ETR (36). These miRNAs are embedded in lncRNA MIR497HG and their downregulation was associated with TAM resistance (37).…”

Section: Discussionmentioning

confidence: 99%

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Suppression of miRs-497/195 axis possibly confers endocrine therapy resistance via elevated expression of FLT4 and the noncoding RNA MIR503HG

Pramanik,

Das,

Mukherjee

et al. 2024

Preprint

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Endocrine therapy resistance (ETR) in breast cancer is achieved by decreasing expression or acquiring mutations in ER, dysregulating cell cycle genes, and/or ER co-activators/co-repressors. We reported that high expression of JMJD6 induced ETR by depleting ER. In this study, RNA-sequencing of parental MCF7, Tamoxifen resistant (TAMR), Long-term Estrogen deprived (LTEDI), and Jumonji domaining containing protein 6 (JMJD6) overexpressing (JOE) cells was carried out. 170 differentially expressed genes common to all cells were found, of which 73 maintained the same directionality in expression. Pathway based curation identified 7 up- and 14 down-regulated genes spanning multiple cancer pathways. These genes were used for CNC and ceRNA network construction and a triad FLT4:MIR503HG:miR497/195/424 was discovered in TAMR-LTED cells, but triads were rare in JOE cells. ER expressing cells probably devise a complex ceRNA based mechanism for ETR establishment, whereas lowering ER is sufficient in JOE cells. Further, the clustering of TCGA samples based on the expression of upregulated ETR genes led to the bifurcation of ER+ tumors into two groups, one intermixing with ER- tumors and showing poorer survival. Of the 7 up genes, B3GNT3, ADORA2B, SLC2A3, and FLT4 showed high expression in ETR models and normal breast but lower expression in tumors. We suggest that re-expression of these genes occurs during therapeutic intervention leading to poorer outcome. In addition to these 4 genes, testing for ER, MIR503HG, miR497, miR195, and miR424 expression could be useful in ETR prediction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Suppression of miRs-497/195 axis possibly confers endocrine therapy resistance via elevated expression of FLT4 and the noncoding RNA MIR503HG

Pramanik,

Das,

Mukherjee

et al. 2024

Preprint

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“…In our opinion, its mechanism may by realized not by directly regulating MIR503HG, but by other indirect signals. MIR503HG interacts with signaling pathways, such as inhibiting the phosphorylated proteins of RAF, MEK, ERK1/2, PI3K and AKT 72 . In view of PI3K inhibitors were determined that could reverse TKIs resistance in tumor 73 , and activated AKT promoting TKIs resistance in RCC 74 , we speculate that MIR503HG-KO cells will be more sensitive to those TKIs than control cells.…”

Section: Discussionmentioning

confidence: 99%

Loss of MIR503HG facilitates papillary renal cell carcinoma associated lymphatic metastasis by triggering NOTCH1/VEGFC signaling

Wang¹,

Zheng²,

Huang³

et al. 2023

Int. J. Biol. Sci.

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Clinical lymphatic metastasis indicates an extremely poor prognosis. Patients with papillary renal cell carcinoma (pRCC) have a high probability of progressing to lymphatic metastasis. However, the molecular mechanism of pRCC-associated lymphatic metastasis has not been elucidated. In this study, we found a downregulated long non-coding RNA (lncRNA) MIR503HG in pRCC primary tumor tissues due to hypermethylation at the CpG islands within its transcriptional start site. Decreased MIR503HG expression could stimulate tube formation and migration of human lymphatic endothelial cell (HLEC) and play a central role to promote lymphatic metastasis in vivo by enhancing tumor lymphangiogenesis. MIR503HG, located in the nucleus, bound with histone variant H2A.Z and affected the recruitment of histone variant H2A.Z to chromatin. Subsequently, increasing the H3K27 trimethylation caused by MIR503HG-overexpression epigenetically downregulated the NOTCH1 expression, which ultimately resulted in decreasing VEGFC secretion and lymphangiogenesis. Additionally, downregulated MIR503HG facilitated the HNRNPC expression, which ultimately promoted the maturation of NOTCH1 mRNA. Notably, upregulating MIR503HG expression might decrease pRCC resistance to the mTOR inhibitor. Together, these findings highlighted a VEGFC-independent mechanism of MIR503HG-mediated lymphatic metastasis. MIR503HG, identified as a novel pRCC-suppressor, would serve as the potentially biomarker for lymphatic metastasis.

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“…One of the stem loops that comprises this junction is also predicted to fold in the nucleoplasm (Supplementary Figure 2C). MIR503HG interacts with several proteins, including polypyrimidine tract binding protein 1 (PTBP1), heterogeneous nuclear ribonucleoproteins HNRNP, A2B1, and specific protein 1 (SP1) to mediate endothelial to mesenchymal transition, regulate hnRNP A2B1 expression, and inhibit activation of TMEFF1, respectively 34,49 . These protein interactions may impact how MIR503HG folds in chromatin and in the nucleoplasm.…”

Section: Mir503hgmentioning

confidence: 99%

Characterization of RBM15 protein binding with long noncoding RNAs

Bose,

Mayes,

Ellis

et al. 2023

Preprint

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Long noncoding ribonucleic acids (lncRNAs) are transcripts greater than 500 nucleotides in length that do not encode for protein. Through their sequences and structures, lncRNAs interact with other nucleic acids and proteins to regulate a variety of biological processes, including gene expression. The rate at which lncRNAs have been identified exceeds our ability to study their structures and functions. Within the last decade, several tens of thousands have been discovered throughout the human genome, yet fewer than 50 have been structurally characterized. In an attempt to better understand and map the vast molecular networks that underlie biological activity, several genome-wide studies have been carried out to study RNA structures, identify their cognate protein binding partners, and map sites of protein binding. Every class of RNA is represented in these studies, including lncRNAs. In this study, we mined this data to investigate the propensity of X-inactivation (XCI) escaping lncRNAs to interact with the RNA binding protein (RBP) RBM15. We find that XCI-escaping lncRNAs are intricately structured and, depending on their localization (cytoplasm, nucleoplasm, chromatin), adopt different structures. Bioinformatic and experimental analyses reveal that U-containing sequences are bound by RNA recognition motifs (RRMs) 2 and 3 of RBM15. Collectively, the mining of data, carried out by graduate students of the New York University Spring 2023 Macromolecular Chemistry course, and the experimental validation of those results, carried out by high school summer interns from traditionally excluded groups, demonstrates i) an efficient way to make use of the genome-wide studies that have been carried out to better understand how lncRNAs function and ii) a way to engage students from a variety of backgrounds in biological research.

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MIR503HG: A potential diagnostic and therapeutic target in human diseases

Cited by 7 publications

References 149 publications

Suppression of miRs-497/195 axis possibly confers endocrine therapy resistance via elevated expression of FLT4 and the noncoding RNA MIR503HG

Suppression of miRs-497/195 axis possibly confers endocrine therapy resistance via elevated expression of FLT4 and the noncoding RNA MIR503HG

Loss of MIR503HG facilitates papillary renal cell carcinoma associated lymphatic metastasis by triggering NOTCH1/VEGFC signaling

Characterization of RBM15 protein binding with long noncoding RNAs

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