HoloMonitor i Nature

10 kinesiska forskare har fått sina studier publicerade i Nature. Det handlar återigen om den förskräckliga cancerformen Glioblastoma. Undertecknad väljer att inte skriva så mkt om denna ruskiga hjärncancer,den är rent ut sagt för jä..lig.

The mechanism of BUD13 m6A methylation mediated MBNL1-phosphorylation by CDK12 regulating the vasculogenic mimicry in glioblastoma cells

Abstract

Vasculogenic mimicry (VM) is an endothelium-independent tumor microcirculation that provides adequate blood supply for tumor growth. The presence of VM greatly hinders the treatment of glioblastoma (GBM) with anti-angiogenic drugs. Therefore, targeting VM formation may be a feasible therapeutic strategy for GBM. The research aimed to evaluate the roles of BUD13, CDK12, MBNL1 in regulating VM formation of GBM. BUD13 and CDK12 were upregulated and MBNL1 was downregulated in GBM tissues and cells. Knockdown of BUD13, CDK12, or overexpression of MBNL1 inhibited GBM VM formation. METTL3 enhanced the stability of BUD13 mRNA and upregulated its expression through m6A methylation. BUD13 enhanced the stability of CDK12 mRNA and upregulated its expression. CDK12 phosphorylated MBNL1, thereby regulating VM formation of GBM. The simultaneous knockdown of BUD13, CDK12, and overexpression of MBNL1 reduced the volume of subcutaneously transplanted tumors in nude mice and prolonged the survival period. Thus, the BUD13/CDK12/MBNL1 axis plays a crucial role in regulating VM formation of GBM and provides a potential target for GBM therapy.

Introduction

Glioblastoma (GBM) is one of the most common primary malignant tumors in the central nervous system [1]. Despite continuous improvement in treatment, the prognosis of GBM remains poor due to the special location and high invasiveness [2], with a median survival of only 15 months. Vasculogenic mimicry (VM) is a new phenomenon about fluid-conducting channels discovered by Maniotis [3]. VM microcirculatory channels lined by nonendothelial cells are generated by pluripotent embryonic stem cells, highly invasive tumor cells and the extra-cellular matrix in aggressive primary and metastatic tumors. VM mimics the function of blood vessels and transports plasma and blood cells, providing an alternative mechanism to supply malignant tumors with adequate blood. The pathological grade of glioma increases with the number of VM [4]. The presence of VM greatly hinders the treatment of GBM with anti-angiogenic drugs [5]. Therefore, it is of great significance to research the inhibition of VM formation in GBM for gene targeting therapy.

Materials and Methods (urval)

Cell migration assay

The capacity for migration in GBM cells was observed by the HoloMonitor M4 culture system (Phase Holographic Imaging PHI AB, Lund, Sweden) in vitro. For details of the experiment, please refer to Supplemental Materials and Methods.

Cell migration assay

Cell migration assay was performed using the HoloMonitor M4 culture system (Phase Holographic Imaging PHI AB, Lund, Sweden) according to the manufacturer’s protocols. The cells of each group were inoculated into a six-well plate at a concentration of 2×10⁴ cells/mL.  After the cells were attached to the culture plate, they were placed on the HoloMonitor M4 culture system and set for imaging for 6 h at 1 h intervals. For each experimental group, we showed the last image frame and cell movements. At the start of the analysis, 5 visually identifiable cells in each experimental set were selected for tracking. Their movements were displayed in spatial X-Y plots.

Min kommentar

Måtte forskarna snabbt hitta botemedel mot denna cancerform. Den är så fruktansvärt elak och ger drabbade så kort tid kvar att leva med dagens botemedel. HoloMonitor har i studien bidragit till att ge forskarna värdefull information att komma närmare en bättre bot. Ni vet vad jag brukar säga, cancerforskning och HoloMonitor hör ihop. Nu får instrumentet uppmärksamhet i Nature vilket är mycket positivt såklart,men hellre ser jag att en bot kommer fram snabbt. 

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