High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma.
High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma.
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高迁移率A2是头颈鳞状细胞癌中miRNA-98的靶标。
DOI：
10.1186/1476-4598-6-5
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发表时间：
2007-01-14
期刊：
影响因子：
37.3
通讯作者：
Sauk, John J
中科院分区：
文献类型：
--
作者：
Hebert, Carla;Norris, Kathleen;Scheper, Mark A;Nikitakis, Nikolaos;Sauk, John J
HMGA2的表达已被证明与癌细胞对拓扑异构酶（topo） II抑制剂阿霉素的选择性化学敏感性增强有关。尽管信号级联反应和蛋白质在发育、肿瘤和环境适应中的调节作用已经得到了很好的证实，但目前越来越多的证据表明，小RNA分子（如microRNAs）是转录和转录后基因沉默的重要调节因子。在这里，我们报道HMGA2在头颈部鳞状细胞癌（HNSCC）细胞中的表达部分受miRNA-98 （miR-98）调节。尽管HMGA2与HNSCC中对拓扑异构酶（topo） II抑制剂阿霉素的选择性化学敏感性增强有关，但HMGA2的表达受到缺氧的抑制。这伴随着miRNA-98和其他可预测靶向HMGA2的mirna的表达增强。此外，我们发现在常氧环境下转染pre-miR-98™会减少HMGA2并增强对阿霉素和顺铂的耐药性。这些发现暗示了miRNA在可变微环境中作为调节肿瘤的关键因素的作用。这些研究证实了HMGA2在控制基因毒性反应中起重要作用的观察结果。然而，这可能只代表在正常氧张力下生长的细胞。miRNA谱在缺氧时发生改变并抑制基因毒性反应的证明表明，真核生物微环境的变化模拟了低等物种和植物的微环境变化，例如，非生物胁迫通过许多miRNA和其他小调控rna在转录和转录后水平上调节植物中数千种基因的表达。
HMGA2 expression has been shown to be associated with enhanced selective chemosensitivity towards the topoisomerase (topo) II inhibitor, doxorubicin, in cancer cells. Although the roles of signaling cascades and proteins as regulatory factors in development, neoplasia and adaptation to the environment are becoming well established, evidence for the involvement of regulatory small RNA molecules, such as microRNAs (miRNAs) as important regulators of both transcriptional and posttranscriptional gene silencing is presently mounting. Here we report that HMGA2 expression in head and neck squamous cell carcinoma (HNSCC) cells is regulated in part by miRNA-98 (miR-98). Albeit HMGA2 is associated with enhanced selective chemosensitivity towards topoisomerase (topo) II inhibitor, doxorubicin in HNSCC, the expression of HMGA2 is thwarted by hypoxia. This is accompanied by enhanced expression of miRNA-98 and other miRNAs, which predictably target HMGA2. Moreover, we show that transfection of pre-miR-98™ during normoxia diminishes HMGA2 and potentiates resistance to doxorubicin and cisplatin. These findings implicate the role of a miRNA as a key element in modulating tumors in variable microenvironments. These studies validate the observation that HMGA2 plays a prominent role in governing genotoxic responses. However, this may only represent cells growing under normal oxygen tensions. The demonstration that miRNA profiles are altered during hypoxia and repress a genotoxic response indicates that changes in microenvironment in eukaryotes mimic those of lower species and plants, where, for example, abiotic stresses regulate the expression of thousands of genes in plants at both transcriptional and posttranscriptional levels through a number of miRNAs and other small regulatory RNAs.