Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 361-763, Republic of Korea.
J Cancer Res Clin Oncol. 2011 Apr;137(4):629-37. doi: 10.1007/s00432-010-0925-5. Epub 2010 Jun 10.
Helicase-like transcription factor (HLTF) is a member of the SWI/SNF (mating type switching/sucrose non-fermenting) family of ATPases/helicases and also has a RING-finger motif characteristic of ubiquitin ligase proteins. These features have led to suggestions that HLTF functions like yeast Rad5, which promotes replication through DNA lesions via a post-replication repair pathway. However, the function of HLTF in higher eukaryotes is still unknown. Herein, we found the overexpression of HLTF in radiation recurrent human uterine cervical carcinoma tissues when compared to disease free survived patients tissues. In this study, we used RNA interference techniques to investigate the potential function of HLTF in cervical cancer cell line HeLa and found that the cell proliferation was reduced by knockdown (KD) of HLTF. A host-cell reactivation assay showed that the capacity for repair to DNA damage induced by X-ray irradiation was reduced in HLTF KD cells. X-rays also increased apoptosis in HLTF KD cells. These results suggest that HLTF is involved in DNA repair and apoptosis in cancer cells, which might represent a target for gene therapies of human cancer.
解旋酶样转录因子（HLTF）是 SWI/SNF（交配型转换/蔗糖非发酵）家族的 ATP 酶/解旋酶成员，并且还具有泛素连接酶蛋白的 RING 指基序特征。这些特征表明 HLTF 的功能类似于酵母 Rad5，后者通过复制后修复途径促进通过 DNA 损伤的复制。然而，HLTF 在高等真核生物中的功能仍然未知。在此，与无病生存的患者组织相比，我们发现辐射复发性人子宫颈癌组织中 HLTF 的过表达。在这项研究中，我们使用 RNA 干扰技术研究了 HLTF 在宫颈癌细胞系 HeLa 中的潜在功能，发现 HLTF 的敲低（KD）降低了细胞增殖。宿主细胞再激活测定表明，HLTF KD 细胞中 X 射线照射诱导的 DNA 损伤的修复能力降低。X 射线还增加了 HLTF KD 细胞的凋亡。这些结果表明 HLTF 参与癌细胞中的 DNA 修复和细胞凋亡，这可能代表人类癌症基因治疗的靶标。
