lncRNA XLOC013218 promotes cell proliferation and TMZ resistance by targeting the PIK3R2-mediated PI3K/AKT pathway in glioma.
lncRNA XLOC013218 promotes cell proliferation and TMZ resistance by targeting the PIK3R2-mediated PI3K/AKT pathway in glioma.
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长链非编码RNA（lncRNA）的发现提高了对各种癌症亚型的发展和进展的理解。然而，lncRNA在多形性胶质母细胞瘤（GBM）中替莫唑胺（TMZ）抗性中的作用在很大程度上仍然不确定。在本研究中，在U87和U87 TMZ耐药（TR）细胞之间鉴定了lncRNA的差异表达。lncRNA XLOC 013218（XcRNA）在TR细胞中显著上调，并且与胶质瘤的不良预后相关。在体外和体内，Xcad的过表达显著增加TMZ抗性，促进增殖，并抑制凋亡。此外，RNA-seq分析和功能获得或功能丧失研究表明，PIK 3R 2是Xcadine的潜在靶点。在机制上，Xcad募集特异性蛋白1（Sp1）转录因子，并促进Sp1与PIK 3R 2启动子的结合，从而在mRNA和蛋白水平上提高PIK 3R 2的表达。最后，PIK 3R 2介导的PI 3 K/AKT信号通路的激活促进TMZ抗性和细胞增殖，但抑制细胞凋亡。总之，这些数据突出了XCR 4/Sp1/PIK 3R 2/PI 3 K/AKT轴在GBM TMZ抗性中的重要作用。lncRNA XLOC 013218（XcRNA）通过以Sp1依赖性方式激活PIK 3R 2介导的PI 3 K/AKT信号通路，促进细胞增殖并抑制细胞凋亡，从而赋予神经胶质瘤替莫唑胺（TMZ）耐药性。
The discovery of long noncoding RNAs (lncRNAs) has improved the understanding of development and progression in various cancer subtypes. However, the role of lncRNAs in temozolomide (TMZ) resistance in glioblastoma multiforme (GBM) remains largely undefined. In this present study, the differential expression of lncRNAs was identified between U87 and U87 TMZ‐resistant (TR) cells. lncRNA XLOC013218 (XLOC) was drastically upregulated in TR cells and was associated with poor prognosis in glioma. Overexpression of XLOC markedly increased TMZ resistance, promoted proliferation, and inhibited apoptosis in vitro and in vivo. In addition, RNA‐seq analysis and gain‐of‐function or loss‐of‐function studies revealed that PIK3R2 was the potential target of XLOC. Mechanistically, XLOC recruited specificity protein 1 (Sp1) transcription factor and promoted the binding of Sp1 to the promoters of PIK3R2, which elevated the expression of PIK3R2 in both mRNA and protein levels. Finally, PIK3R2‐mediated activation of the PI3K/AKT signaling pathway promoted TMZ resistance and cell proliferation, but inhibited cell apoptosis. In conclusion, these data highlight the vital role of the XLOC/Sp1/PIK3R2/PI3K/AKT axis in GBM TMZ resistance. lncRNA XLOC013218 (XLOC) confers temozolomide (TMZ) resistance of glioma by promoting cell proliferation and inhibiting cell apoptosis via activation of the PIK3R2‐mediated PI3K/AKT signaling pathway in an Sp1‐dependent manner.
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影响因子：
5.3
作者：
Fu Rao;Tong Jing-Shan
通讯作者：
Tong Jing-Shan
Forkhead box D1 通过上调口腔鳞状细胞癌中的 lncRNA CYTOR 促进 EMT 和化疗耐药
影响因子：
9.7
作者：
Chen, Shuwei;Yang, Muwen;Zhang, Quan
通讯作者：
Zhang, Quan
影响因子：
12.4
作者：
Li, Tao;Yang, Xiaoshuang;Liu, Ying
通讯作者：
Liu, Ying
影响因子：
14.9
作者：
McCarthy DJ;Chen Y;Smyth GK
通讯作者：
Smyth GK
DOI：
10.1038/s41580-020-00315-9
发表时间：
2021-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Statello L;Guo CJ;Chen LL;Huarte M
通讯作者：
Huarte M