A novel lncRNA ARST represses glioma progression by inhibiting ALDOA-mediated actin cytoskeleton integrity.
A novel lncRNA ARST represses glioma progression by inhibiting ALDOA-mediated actin cytoskeleton integrity.
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一种新型 lncRNA ARST 通过抑制 ALDOA 介导的肌动蛋白细胞骨架完整性来抑制神经胶质瘤进展
DOI：
10.1186/s13046-021-01977-9
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发表时间：
2021-06-07
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Sun J;He D;Fu Y;Zhang R;Guo H;Wang Z;Wang Y;Gao T;Wei Y;Guo Y;Pang Q;Liu Q
胶质瘤是最具侵袭性的脑恶性肿瘤之一，其特点是不可避免的浸润性生长和预后差。ARST是一种新的lncRNA，其在多形性胶质母细胞瘤患者中的表达水平显著降低。然而，ARST在胶质瘤发生中的确切机制在很大程度上是未知的。通过qRT-PCR分析ARST在胶质瘤样品和细胞系中的表达。用荧光原位杂交技术检测ARST在胶质瘤细胞中的分布。CCK-8、EdU和流式细胞术检测细胞活力、增殖和凋亡。进行Transwell和伤口愈合测定以确定细胞的迁移和侵袭能力。建立颅内肿瘤发生模型，探讨ARST在体内的作用。RNA pulldown分析用于检测与ARST结合的蛋白质。用比色法测定了糖酵解和乳酸生成过程中关键酶的活性。此外，还采用RIP、Co-IP、Western blot和免疫荧光等方法研究了ARST、F-actin、ALDOA和cofilin之间的相互作用和调控。在这项研究中，我们报道了ARST在胶质瘤中下调。ARST在胶质瘤细胞中的过表达显著抑制了细胞的生长、增殖、迁移和侵袭等多种生命能力。这些细胞在体内的致瘤能力也降低。我们进一步证明，ARST的肿瘤抑制作用可能是通过直接结合糖酵解酶醛缩酶A（ALDOA）介导的，ALDOA与cofilin一起保持肌动蛋白丝的聚合和解聚处于有序的动态平衡。ARST的上调中断了ALDOA和肌动蛋白细胞骨架之间的相互作用，这导致了F-actin应力纤维的快速cofilin依赖性损失。两者合计，可以得出结论，ARST通过与ALDOA相关的非代谢途径发挥其功能，否则会改变胶质瘤细胞的形态和侵袭性。这为研究其在肿瘤发生中的作用提供了新的视角，为胶质瘤的诊断、治疗和预后提供了潜在的靶点。在线版本包含补充材料，可通过10.1186/s13046-021-01977-9获得。
Glioma is one of the most aggressive malignant brain tumors that is characterized with inevitably infiltrative growth and poor prognosis. ARST is a novel lncRNA whose expression level is significantly decreased in the patients with glioblastoma multiforme. However, the exact mechanisms of ARST in gliomagenesis are largely unknown. The expressions of ARST in the glioma samples and cell lines were analyzed by qRT-PCR. FISH was utilized to detect the distribution of ARST in the glioma cells. CCK-8, EdU and flow cytometry were used to examine cellular viability, proliferation and apoptosis. Transwell and wound-healing assays were performed to determine the migratory and invasive abilities of the cells. Intracranial tumorigenesis models were established to explore the roles of ARST in vivo. RNA pulldown assay was used to examine proteins that bound to ARST. The activities of key enzymes in the glycolysis and production of lactate acid were measured by colorimetry. In addition, RIP, Co-IP, western blot and immunofluorescence were used to investigate the interaction and regulation between ARST, F-actin, ALDOA and cofilin. In this study, we reported that ARST was downregulated in the gliomas. Overexpression of ARST in the glioma cells significantly suppressed various cellular vital abilities such as cell growth, proliferation, migration and invasion. The tumorigenic capacity of these cells in vivo was reduced as well. We further demonstrated that the tumor suppressive effects of ARST could be mediated by a direct binding to a glycolytic enzyme aldolase A (ALDOA), which together with cofilin, keeping the polymerization and depolymerization of actin filaments in an orderly dynamic equilibrium. Upregulation of ARST interrupted the interaction between ALDOA and actin cytoskeleton, which led to a rapid cofilin-dependent loss of F-actin stress fibers. Taken together, it is concluded that ARST performs its function via a non-metabolic pathway associated with ALDOA, which otherwise modifies the morphology and invasive properties of the glioma cells. This has added new perspective to its role in tumorigenesis, thus providing potential target for glioma diagnosis, therapy, and prognosis. The online version contains supplementary material available at 10.1186/s13046-021-01977-9.
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影响因子：
--
作者：
MONCMAN, CL;PENG, I;WINKELMANN, DA
通讯作者：
WINKELMANN, DA
影响因子：
9.7
作者：
Peng, Wen;Zhang, Chuan;Sun, Yueming
通讯作者：
Sun, Yueming
DOI：
10.1093/bioinformatics/btr209
发表时间：
2011-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Lin MF;Jungreis I;Kellis M
通讯作者：
Kellis M
影响因子：
48
作者：
Wisniewski, Jacek R.;Zougman, Alexandre;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
3.2
作者：
Islam SMA;Patel R;Bommareddy RR;Khalid KM;Acevedo-Duncan M
通讯作者：
Acevedo-Duncan M