Upregulated miRNA-622 inhibited cell proliferation, motility, and invasion via repressing Kirsten rat sarcoma in glioblastoma

Wang, Xinzhi; Xin, Zhen-xue; Xu, Yinfu; Ma, Jinbang

doi:10.1007/s13277-015-4455-2

Cited by 20 publications

(8 citation statements)

References 26 publications

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“…Only one target gene—KRAS—was depicted as “validated by strong evidence methods” (i.e., Western blot or “reporter” assay) (Figure a). Indeed, KRAS had been experimentally validated to be a functional target gene for miR‐622 in glioblastoma (Wang, Xin, Xu, & Ma, ).…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‐622 is a novel mediator of tumorigenicity in melanoma by targeting Kirsten rat sarcoma

Dietrich

Kuphal

Spruß

et al. 2018

Pigment Cell Melanoma Res

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The network of molecular players is similar when comparing neural crest-derived, actively migrating melanoblasts to melanoma cells. However, melanoblasts are sensitive to differentiation-initiating signals at their target site (epidermis), while melanoma cells maintain migratory and undifferentiated features. We aimed at identifying downregulated genes in melanoma that are particularly upregulated in melanoblasts. Loss of such genes could contribute to stabilization of a dedifferentiated, malignant phenotype in melanoma. We determined that microRNA-622 (miR-622) expression was strongly downregulated in melanoma cells and tissues compared to melanocytes and melanoblast-related cells. miR-622 expression correlated with survival of patients with melanoma. miR-622 re-expression inhibited clonogenicity, proliferation, and migration in melanoma. Inhibition of miR-622 in melanocytes induced enhanced migration. Kirsten rat sarcoma (KRAS) was identified as a major functional target of miR-622 in melanoma. We conclude that miR-622 is a novel tumor suppressor in melanoma and identify the miR-622-KRAS axis as potential therapeutic target.

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Section: Resultsmentioning

confidence: 99%

MicroRNA‐622 is a novel mediator of tumorigenicity in melanoma by targeting Kirsten rat sarcoma

Dietrich

Kuphal

Spruß

et al. 2018

Pigment Cell Melanoma Res

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“…A172 cells, which display mesenchymal morphology and aggressive cell growth [29, 30], had higher levels of ASPH expression (∼86 kDa) than U87 cells; however Humbug, which mediates calcium flux from the ER, was more abundantly expressed in U87 compared with A172 cells (Fig. 6A).…”

Section: Resultsmentioning

confidence: 99%

Aspartate-β-hydroxylase (ASPH): A potential therapeutic target in human malignant gliomas

Sturla

Tong

Hebda

et al. 2016

Heliyon

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BackgroundDespite therapeutic advances, survival with glioblastoma multiforme (GBM) remains below 15 months from diagnosis due to GBM’s highly infiltrative nature which precludes complete surgical resection. Patient outcomes could potentially be improved by targeting genes and pathways that drive neoplastic cell motility and invasiveness, including hypoxia-inducible factor-1 (HIF-1α), NOTCH, and aspartate-β-hydroxylase (ASPH).MethodsHuman astrocytoma biopsy specimens (n = 37), WHO Grades II–IV, were analyzed for levels and distributions of ASPH and HIF-1α immunoreactivity by immunohistochemical staining, and ASPH, Notch, JAG, HES1, HEY1 and HIF1α mRNA expression by quantigene multiplex analysis. The effects of small molecule inhibitors on ASPH’s catalytic activity, cell viability and directional motility were examined in vitro in established GBM cell lines and primary tumor cells from an invasive mouse model of GBM.ResultsThe highest grade astrocytoma, i.e. GBM was associated with the highest levels of ASPH and HIF1α, and both proteins were more abundantly distributed in hypoxic compared with normoxic regions of tumor. Furthermore, mining of the TCGA database revealed higher levels of ASPH expression in the mesenchymal subtype of GBM, which is associated with more aggressive and invasive behavior. In contrast, lower grade astrocytomas had low expression levels of ASPH and HIF1α. In vitro experiments demonstrated that small molecule inhibitors targeting ASPH’s catalytic activity significantly reduced GBM viability and directional motility. Similar effects occurred in GBM cells that were transduced with a lentiviral sh-ASPH construct.ConclusionThis study demonstrates that increased ASPH expression could serve as a prognostic biomarker of gliomas and may assist in assigning tumor grade when biopsy specimens are scant. In addition, the findings suggest that GBM treatment strategies could be made more effective by including small molecule inhibitors of ASPH.

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“…miRNAs can regulate cell proliferation, invasion, migration, the cell cycle and apoptosis (20), as well as regulating transcription through RNA polymerase, to impact tumor development (21,22). Previous studies indicated that aberrant expression of miRNAs has been identified in a number of types of cancer, including stomach, liver, colorectal, breast and cervical cancer, as well as glioma and others (23,24).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑181 inhibits glioblastoma cell growth by directly targeting CCL8

Zhai

Chen

et al. 2019

Oncol Lett

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MicroRNAs (miRNAs/miRs), including miR-181, are closely linked to the development and progression of glioblastoma. However, the function of miR-181 in glioblastoma has not been fully clarified. The aim of the present study was to investigate the role of miR-181 in glioblastoma. miR-181 was revealed to be downregulated in glioblastoma tissues and cell lines, and associated with poor prognosis in patients with glioblastoma. Overexpression of miR-181 inhibited glioblastoma cell proliferation, invasion and migration, arrested glioblastoma cell cycle in the G1 phase and induced glioblastoma cell apoptosis. miR-181 was demonstrated to decrease expression of C-C motif chemokine ligand 8 (CCL8) by directly interacting with its 3′-untranslated region. Overexpression of CCL8 inversely reversed the proliferation, invasion and migration-promoting effects of miR-181 in glioblastoma cells. Furthermore, CCL8 was upregulated in glioblastoma tissues and was negatively correlated with miR-181 expression. These results indicate that miR-181 is a potential molecular biomarker or therapeutic target in the clinical management of glioblastoma.

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Upregulated miRNA-622 inhibited cell proliferation, motility, and invasion via repressing Kirsten rat sarcoma in glioblastoma

Cited by 20 publications

References 26 publications

MicroRNA‐622 is a novel mediator of tumorigenicity in melanoma by targeting Kirsten rat sarcoma

MicroRNA‐622 is a novel mediator of tumorigenicity in melanoma by targeting Kirsten rat sarcoma

Aspartate-β-hydroxylase (ASPH): A potential therapeutic target in human malignant gliomas

MicroRNA‑181 inhibits glioblastoma cell growth by directly targeting CCL8

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