2020
DOI: 10.1038/s41598-019-56983-x
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MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

Abstract: Glioblastoma (GBM) is an astrocytic brain tumor with median survival times of <15 months, primarily as a result of high infiltrative potential and development of resistance to therapy (i.e., surgical resection, chemoradiotherapy). A prominent feature of the GBM microenvironment is compressive solid stress (CSS) caused by uninhibited tumor growth within the confined skull. Here, we utilized a mechanical compression model to apply cSS (<115 Pa) to well-characterized LN229 and U251 GBM cell lines and measured the… Show more

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Cited by 16 publications
(17 citation statements)
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“…Thus, mir-548 downregulation is required for cell proliferation has been associated with increased glioblastoma cell motility and could be a predictor for progression of neuroblastomas 100,101 . High levels of Mir-548 have been found patients with early-onset Myasthenia Gravis 102 .…”
Section: Discussionmentioning
confidence: 99%
“…Thus, mir-548 downregulation is required for cell proliferation has been associated with increased glioblastoma cell motility and could be a predictor for progression of neuroblastomas 100,101 . High levels of Mir-548 have been found patients with early-onset Myasthenia Gravis 102 .…”
Section: Discussionmentioning
confidence: 99%
“…Compressive forces are physical forces that have a net inward vector on an object. Compressive forces in GBM produce a range of physiological responses from the tumor, leading to the induction of migration, the upregulation of epigenetic signals, and the formation of new blood vessels [ 14 , 15 , 16 ]. In U87 and HGL21 cell lines, compression strain induced the downregulation of E-cadherin (CDH1) and PECAM-1 (CD31) and the upregulation of PTEN and Rac1.…”
Section: Discussionmentioning
confidence: 99%
“…In the Ln229 and U251 GBM lines, mechanical compression led to miR548 family induction of epigenetic signaling. The induced signaling was correlated to cell elongation, increased migration, decreased proliferation, and increased tumor aggression characteristics [ 15 ]. The induced mechanical compression in the study by Calhoun et al was also associated with decreased survival and increased therapy resistance, which they suggest may be due to the enhanced migration and escape mechanisms from focal surgical or chemotherapeutic treatment [ 15 ].…”
Section: Discussionmentioning
confidence: 99%
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“…A wound healing system with compression with a rigid weight disc on an agar cushion on top of glioblastoma cells was used to mimic solid stress of cells detaching from the tumor within a confined skull. Results revealed a link between miR548 and increased migration as well as an influence on genes associated with chemoresistance ( TMEM45Q ) and angiogenesis ( CTGF , VEGFA, VEGFB ) ( Calhoun et al, 2020 ). However, these results were obtained with different types of matrices, which makes it difficult to identify strict mechanical impact from a combination of mechanical and biochemical signaling.…”
Section: A Bright Future For 3d Cell Culture In Mechanomedicinementioning
confidence: 99%