<i>miR‐29b</i> and <i>miR‐125a</i> regulate podoplanin and suppress invasion in glioblastoma

Cortez, María Angélica; Nicoloso, Milena S.; Shimizu, Masayoshi; Rossi, Simona; Gopisetty, Gopal; Molina, Jennifer R.; Carlotti, Carlos Gilberto; Tirapelli, Daniela Pretti da Cunha; Neder, Luciano; Brassesco, María Sol; Scrideli, Carlos Alberto; Tone, Luíz Gonzaga; Georgescu, Maria Magdalena; Zhang, Wei; Puduvalli, Vinay K.; Calin, George A.

doi:10.1002/gcc.20808

Cited by 126 publications

(107 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4 miRNA dysregulation is a common feature of neoplasia and numerous miRNAs have been characterized as oncogenes or tumor suppressors in many cancers including in glioblastoma (GBM). 3,[5][6][7][8][9][10][11] microRNA-134 (miR-134) has been implicated in the regulation of physiological and developmental processes. It was shown to promote mouse embryonic stem-cell differentiation, dendritogenesis, and stage-specific cortical development.…”

mentioning

confidence: 99%

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

Zhang

Mueller

et al. 2014

Cell Death Differ

View full text Add to dashboard Cite

Receptor tyrosine kinases (RTKs) are co-deregulated in a majority of glioblastoma (GBM), the most common and most deadly brain tumor. We show that the RTKs MET, EGFR, and PDGFR regulate microRNA-134 (miR-134) in GBM. We find that miR-134 is downregulated in human tumors and cancer stem cells and that its expression inversely correlates with the activation of MET, EGFR, and PDGFR. We demonstrate that miR-134 inhibits cancer cell and stem-cell proliferation, survival, and xenograft growth, as well as cancer stem-cell self-renewal and stemness. We identify KRAS and STAT5B as targets of miR-134, and establish molecular and functional links between RTKs, miR-134, KRAS/STAT5B and malignancy in vitro and in vivo. We show that miR-134 induction is required for the anti-tumor effects of RTK inhibitors. We also uncover the molecular pathways through which RTKs regulate miR-134 expression and demonstrate the involvement of MAPK signaling and the KLF4 transcription factor. We therefore identify miR-134 as a novel RTK-regulated tumor-suppressive hub that mediates RTK and RTK-inhibitor effects on GBM malignancy by controlling KRAS and STAT5B. Cell Death and Differentiation (2014) 21, 720-734; doi:10.1038/cdd.2013; published online 17 January 2014 microRNAs (miRNAs) regulate a wide variety of physiological and pathological processes. 1-3 miRNAs modulate protein expression by binding to the 3 0 untranslated region (3 0 UTR) of target mRNA and promoting RNA degradation and/or inhibiting translation. Single miRNAs can regulate multiple molecules, highlighting a powerful mechanism for the regulation of redundant and cross-talking signal transduction pathways. 4 miRNA dysregulation is a common feature of neoplasia and numerous miRNAs have been characterized as oncogenes or tumor suppressors in many cancers including in glioblastoma (GBM). 3,[5][6][7][8][9][10][11] microRNA-134 (miR-134) has been implicated in the regulation of physiological and developmental processes. It was shown to promote mouse embryonic stem-cell differentiation, dendritogenesis, and stage-specific cortical development. 12-17 miR-134 is downregulated by SIRT1 and involved in synaptic plasticity and memory formation. 18 miR-134 expression is regulated by MEF2 in dendritogenesis 14 and GBM. 19 GBM is the most common and most deadly primary malignant brain tumor. 20,21 The Cancer Genome Atlas and other studies have shown that aberrant expression or activation of the receptor tyrosine kinases (RTKs) EGFR, MET, and PDGFR occurs in a majority of GBM and correlates with poor prognosis. 22 Importantly, multiple RTKs are co-activated in the same GBM tumors and tumor cells. 23,24 KRAS, STAT3, and STAT5 are activated by RTKs and mediate their oncogenic effects. [25][26][27][28] The failure of current treatments for GBM is arguably due to the presence in the tumors of GBM stem cells (GSCs) that are resistant to radioand chemo-therapy and capable of maintaining and propagating the tumors. 29-31 EGFR, MET, PDGFR, and miRNAs have been implicated in the regulation of GSC f...

show abstract

mentioning

confidence: 99%

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

Zhang

Mueller

et al. 2014

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…In addition, results from the wound‐healing assay revealed that transfection of miR‐29b‐3p mimic significantly prevented the repair of cell scratch injury, suggesting the reduction of damage repair capacity of these cell types. Although no direct evidence shows miR‐29b‐3p could accelerate chondrocyte apoptosis at present, the inducing effect of miR‐29 family on apoptosis and cell cycle arrest has been described in a variety of tumour cell types and some normal cell types, including chronic myelogenous leukaemia cells 29, glioblastoma cells 30, neuronal cell 31 and multiple myeloma cells 32, and the mechanisms were usually associated with the regulation of BCR/ABL1, Mcl‐1, Bcl2. In this work, we observed that miR‐29b‐3p mimic could facilitate Bax expression, restrain Bcl2 expression and promote the activation of caspase‐3, which may contribute to the cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN

Chen

Wang

et al. 2017

J Cellular Molecular Medi

111

View full text Add to dashboard Cite

This study was aimed to explore the role of miR‐29b‐3p and PGRN in chondrocyte apoptosis and the initiation and progress of osteoarthritis (OA). Both miR‐29b‐3p and PGRN were up‐regulated in cartilage tissue from patients with OA. Transfection of miR‐29b‐3p mimic into rat primary chondrocytes and SW1353 chondrosarcoma cells significantly suppressed PGRN expression and release, induced apoptosis, inhibited proliferation and scratch wound closure. By contrast, transfection of miR‐29b‐3p inhibitor exhibited the opposite effects. Moreover, the expression and secretion of cartilaginous degeneration‐related molecules were also altered by miR‐29b‐3p. Luciferase reporter gene assay showed rat GRN mRNA is directly targeted and repressed by miR‐29b‐3p. The fact that recombinant PGRN or shPGRN‐mediated PGRN interference abolished miR‐29b‐3p mimic‐induced cell apoptosis and growth inhibition suggested miR‐29b‐3p affect the cellular functions of chondrocyte through regulating PGRN expression. In vivo, joint cavity injection of miR‐29b‐3p antagomir prior to surgical induction of OA significantly suppressed the upregulation of miR‐29b‐3p, whereas further promoted the increased expression of PGRN. Articular chondrocytes apoptosis and cartilage loss in the knee joint of surgically induced OA rats were also ameliorated by the injection of miR‐29b‐3p antagomir, demonstrated by TUNEL and safranin O‐fast green staining. This work showed miR‐29b‐3p facilitates chondrocyte apoptosis and OA by targeting PGRN, and miR‐29b‐3p or PGRN may be the potential target for OA treatments.

show abstract

“…PDPN expression enhances the motility and invasion of several transformed cell types including mammary carcinoma (7,8), glioma (28), and squamous carcinoma cells (29 -31). PDPN is found at the invasive front of many tumors, which is consistent with its role in promoting invasion (7,8).…”

Section: Discussionmentioning

confidence: 99%

Serines in the Intracellular Tail of Podoplanin (PDPN) Regulate Cell Motility

Krishnan¹,

Ochoa-Alvarez²,

Shen³

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: PDPN is a transmembrane receptor that promotes cell migration, but modifications that regulate its effects are not known. Results: PKA can phosphorylate PDPN, nonphosphorylatable PDPN promotes cell migration, and phosphomimetic PDPN fails to promote cell migration. Conclusion: PKA can phosphorylate PDPN to decrease cell migration. Significance: PDPN effects on cell motility are important for processes including embryonic development and cancer progression.

show abstract

miR‐29b and miR‐125a regulate podoplanin and suppress invasion in glioblastoma

Cited by 126 publications

References 42 publications

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN

Serines in the Intracellular Tail of Podoplanin (PDPN) Regulate Cell Motility

Contact Info

Product

Resources

About