miR-15a and miR-16 affect the angiogenesis of multiple myeloma by targeting VEGF

Sun, Chaoyang; She, Xiao-Mei; Qin, You; Chu, Zhang-Bo; Chen, Lei; Ai, Lisha; Zhang, Lu; Hu, Yu

doi:10.1093/carcin/bgs333

Cited by 188 publications

(141 citation statements)

References 52 publications

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“…53 In addition, both miRNAs were shown to directly regulate VEGF-A expression during MM progression, inhibiting angiogenesis and decreasing miRNAs as regulators of bone homeostasis and metastasis B Ell and Y Kang tumor growth in vivo. 54 Conversely, miR-221 and miR-222 were frequently upregulated in MM patients, and expression of miRNA inhibitors to miR-221/222 decreased the proliferation and tumorigenesis of MM cells in vitro and in vivo. 55 …”

Section: Regulation Of Multiple Myeloma Via Mirnasmentioning

confidence: 99%

MicroRNAs as regulators of bone homeostasis and bone metastasis

Ell

Kang

2014

Bonekey Reports

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MicroRNAs (miRNAs) are short, endogenous RNAs that have essential roles in regulating gene expression through the disruption of target genes. The miRNA-induced suppression can occur through Argonaute-mediated cleavage of target mRNAs or by translational inhibition. System-wide studies have underscored the integral role that miRNAs play in regulating the expression of essential genes within bone marrow stromal cells. The miRNA expression has been shown to enhance or inhibit cell differentiation and activity, and elucidating miRNA targets within bone marrow cells has revealed novel regulations during normal bone development. Importantly, multiple studies have shown that miRNA misexpression mediates the progression of bone-related pathologies, including osteopetrosis and osteoporosis, as well as the development and progression of osteosarcoma. Furthermore, recent studies have detailed the capacity for miRNAs to influence bone metastasis from a number of primary carcinomas. Taken together, these findings reveal the significant clinical potential for miRNAs to regulate bone homeostasis, as well as to mediate bone-related pathologies.BoneKEy Reports 3, Article number: 549 (2014) | doi:10.1038/bonekey.2014.44 MiRNA Biogenesis and FunctionThe past decade has seen a torrent of novel research into the post-translational regulation of genes via microRNA-mediated suppression. The microRNAs (miRNAs) are a class of B22-nucleotide-long RNAs that repress gene expression through complementary binding to sites in the 3 0 -untranslated region (UTR) of target mRNAs. 1 Mature miRNAs are generated by the sequential cleavage of longer precursor transcripts, or pri-miRNAs, that are typically transcribed from intragenic or intergenic regions by RNA polymerase II. 2 The initial cleavage step, mediated by Drosha and the DGCR8 complex, occurs in the nucleus and produces a shortened (70-100 nucleotides) pre-miRNA hairpin. Pre-miRNAs are exported from the nucleus by Exportin 5, followed by a second cleavage by the ribonuclease Dicer that produces a double-stranded, B18-25-nucleotide-long mature miRNA. One miRNA strand will then combine with Argonaute (AGO2) proteins to produce an RNAinduced silencing complex, allowing for directed pairing with target mRNAs. 1

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Section: Regulation Of Multiple Myeloma Via Mirnasmentioning

confidence: 99%

MicroRNAs as regulators of bone homeostasis and bone metastasis

Ell

Kang

2014

Bonekey Reports

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“…Previous studies have reported that miR-15a and miR-16 downregulated in several types of cancer, including MM (8,19). Overexpression of CABIN1 is associated with poorer patient outcomes in a number of cancer types (18,20,21).…”

Section: Upregulation Of Mir-15a and Mir-16 Inhibits The Proliferatiomentioning

confidence: 97%

“…1B). (8,19). To determine whether miR-15a and miR-16 are capable of targeting and regulating CABIN1 expression in MM, a gain-of-function study was performed.…”

Section: Mir-15a/16 Have Potential Target Sites On Cabin1 Mrnamentioning

confidence: 99%

“…miRNAs modulate regulatory cell pathways by influencing target genes and may serve crucial functions in oncogenesis (5). Evidence indicates that miRNAs regulate MM tumorigenesis and can be valuable markers for predicting diagnosis, risk stratification and clinical outcomes (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…miR-15a and miR16 are clustered at chromosomal location 13q14 and possess similar sequences; they are considered to have similar tumor suppressor functions and to be involved in the regulation of cell differentiation, proliferation, apoptosis or angiogenesis in several types of human cancer, including MM (8)(9)(10)(11)(12). Previous studies have indicated that miR-15a/16-1 downregulation contributes to myeloma pathogenesis and mediates drug resistance in myeloma cells (13,14).…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of miRNA‑15a and miRNA‑16 promote tumor proliferation in multiple myeloma by increasing CABIN1 expression

et al. 2017

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Abstract. Multiple myeloma (MM) is a malignant disorder characterized by the neoplastic growth of plasma cells in the bone marrow. MicroRNAs (miRNAs/miRs) modulate key regulatory cell pathways via their influence on target genes, and may serve a crucial function in tumorigenesis. Previous studies have indicated that the downregulation of miR-15a and miR-16 contributes to MM pathogenesis. However, the functional mechanisms of miR-15a and miR-16 in MM remain unclear. In the present study, potential target sites for miR-15a and miR-16 were identified on the calcineurin-binding protein 1 (CABIN1) mRNA sequence from analyses of previously published crosslinking, ligation and sequencing of hybrids data. Again-of-function study was also performed, which determined that miR-15a/16 directly targeted CABIN1 mRNA and negatively regulated the expression of CABIN1 at the mRNA and protein level in MM cells. A cell proliferation assay demonstrated that the upregulation of miR-15a and miR-16 inhibited the proliferation of MM cells via targeting CABIN1. miR-15a and miR-16 were significantly decreased in MM specimens, compared with in normal specimens, whereas CABIN1 mRNA levels were significantly higher in MM samples compared with in normal samples. CABIN1 mRNA levels were negatively correlated with miR-15a and miR-16 expression levels in MM tissues, as determined using Pearson's correlation coefficient analysis. The results of the present study indicate that the downregulation of miR-15a and miR-16 promotes tumor proliferation in MM by increasing CABIN1 expression. The present study may aid elucidation of the functions of miR-15a and miR-16 and their function in MM carcinogenesis.

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Thyroid Hormone, Hormone Analogs, and Angiogenesis

Davis

Sudha

Lin

et al. 2015

Comprehensive Physiology

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Modulation by thyroid hormone and hormone analogs of angiogenesis in the heart after experimental infarction, and in other organs, has been appreciated for decades. Description of a plasma membrane receptor for thyroid hormone on the extracellular domain of integrin αvβ3 on endothelial cells has revealed the complexity of the nongenomic regulation of angiogenesis by the hormone. From αvβ3, the hormone directs transcription of specific vascular growth factor genes, regulates growth factor receptor/growth factor interactions and stimulates endothelial cell migration to a vitronectin cue; these actions are implicated experimentally in tumor-relevant angiogenesis and angioproliferative pulmonary hypertension. Derived from L-thyroxine (T4), tetraiodothyroacetic acid (tetrac) can be covalently bound to a polymer and as Nanotetrac acts exclusively at the hormone receptor on αvβ3 to block actions of T4 and 3,5,3'-triiodo-L-thyronine (T3) on angiogenesis. Other antiangiogenic actions of Nanotetrac include disruption of crosstalk between integrin αvβ3 and adjacent cell surface vascular growth factor receptors, resulting in disordered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF; FGF2) actions at their respective plasma membrane receptors. From αvβ3, Nanotetrac also downregulates expression of VEGFA and epidermal growth factor receptor (EGFR) genes, upregulates transcription of the angiogenesis suppressor gene, thrombospondin 1 (THBS1; TSP1) and decreases cellular abundance of Ang-2 protein and matrix metalloproteinase-9. Existence of this receptor provides new insights into the multiple mechanisms by which thyroid hormone and hormone analogs may regulate angiogenesis at the molecular level. The receptor also offers pharmacological opportunities for interruption of pathological angiogenesis via integrin αvβ3.

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miR-15a and miR-16 affect the angiogenesis of multiple myeloma by targeting VEGF

Cited by 188 publications

References 52 publications

MicroRNAs as regulators of bone homeostasis and bone metastasis

MicroRNAs as regulators of bone homeostasis and bone metastasis

Downregulation of miRNA‑15a and miRNA‑16 promote tumor proliferation in multiple myeloma by increasing CABIN1 expression

Thyroid Hormone, Hormone Analogs, and Angiogenesis

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