International Centre for Genetic Engineering and Biotechnology Padriciano 99, 34149 Trieste, Italy.
Mol Cancer. 2011 Jul 13;10:83. doi: 10.1186/1476-4598-10-83.
RecQ helicases play an essential role in the maintenance of genome stability. In humans, loss of RecQ helicase function is linked with predisposition to cancer and/or premature ageing. Current data show that the specific depletion of the human RECQ1 helicase leads to mitotic catastrophe in cancer cells and inhibition of tumor growth in mice.
Here, we show that RECQ1 is highly expressed in various types of solid tumors. However, only in the case of brain gliomas, the high expression of RECQ1 in glioblastoma tissues is paralleled by a lower expression in the control samples due to the poor expression of RECQ1 in non-dividing tissues. This conclusion is validated by immunohistochemical analysis of a tissue microarray containing 63 primary glioblastomas and 19 perilesional tissue samples, as control. We also show that acute depletion of RECQ1 by RNAi results in a significant reduction of cellular proliferation, perturbation of S-phase progression, and spontaneous γ-H2AX foci formation in T98G and U-87 glioblastoma cells. Moreover, RECQ1 depleted T98G and U-87 cells are hypersensitive to HU or temozolomide treatment.
Collectively, these results indicate that RECQ1 has a unique and important role in the maintenance of genome integrity. Our results also suggest that RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas.
RecQ 解旋酶在维持基因组稳定性方面起着至关重要的作用。在人类中，RecQ 解旋酶功能的丧失与癌症易感性和/或早衰有关。目前的数据表明，人 RECQ1 解旋酶的特异性耗竭会导致癌细胞有丝分裂灾难，并抑制小鼠肿瘤生长。
在这里，我们表明 RECQ1 在各种类型的实体瘤中高度表达。然而，只有在脑胶质瘤的情况下，由于 RECQ1 在非分裂组织中的低表达，高表达的 RECQ1 在胶质母细胞瘤组织中与对照样本中的低表达相平行。通过包含 63 例原发性胶质母细胞瘤和 19 例病变周围组织样本的组织微阵列的免疫组织化学分析验证了这一结论，作为对照。我们还表明，通过 RNAi 急性耗竭 RECQ1 会导致 T98G 和 U-87 胶质母细胞瘤细胞的细胞增殖显著减少、S 期进程受到干扰，并自发形成 γ-H2AX 焦点。此外，RECQ1 耗尽的 T98G 和 U-87 细胞对 HU 或替莫唑胺治疗敏感。
总之，这些结果表明 RECQ1 在维持基因组完整性方面具有独特而重要的作用。我们的结果还表明，RECQ1 可能代表一种新的适合用于针对脑胶质瘤细胞增殖的抗癌治疗的合适靶点。
