Department of Cell Biology, School of Medicine, Soochow University, Suzhou, 215123 China.
Int J Biol Sci. 2013 Jul 5;9(6):637-48. doi: 10.7150/ijbs.6439. Print 2013.
RMP has been shown to function in the transcription regulation through association with RNA polymerase (RNAP) II subunit RPB5. It also has been shown to be required for the proliferation of hepatocellular carcinoma (HCC) cells with an antiapoptotic property. In this article, we further demonstrate that RMP displays distinct features in HCC cells compared with normal hepatic cells. RMP expression is remarkably increased in various cancer cell lines including HCC cells when compared with normal cells. Depletion of RMP could inhibit the proliferation of HCC cells, but not the normal hepatic cells. RMP significantly prevented apoptosis of HCC cells in SMMC-7721 and HepG2, but had little effect on apoptosis in the normal hepatic cells. The mechanisms of RMP's distinct features rely on different responsive expressions of apoptosis factors induced by RMP in HCC and hepatic cells. Either overexpression or depletion of RMP significantly affected the expression of apoptosis factors in HCC cells. However, normal hepatic cells showed a tendency to resist RMP for the regulation of apoptosis. In the clinical samples, the increased expression of RMP in HCCs was also observed when compared with the matched non-tumor tissues from 30 HCC patients. The different expression levels of and distinct responses to RMP between HCC and hepatic cells suggest that RMP might serve as not only a biomarker for the diagnosis of HCC, but also a potential target for the HCC therapy.
RMP 通过与 RNA 聚合酶(RNAP)II 亚基 RPB5 结合,在转录调控中发挥作用。它还被证明具有抗细胞凋亡特性,是肝癌(HCC)细胞增殖所必需的。在本文中,我们进一步证明了 RMP 在 HCC 细胞中与正常肝细胞具有明显不同的特征。与正常细胞相比,RMP 在各种癌细胞系(包括 HCC 细胞)中的表达显著增加。与正常肝细胞相比,RMP 的耗竭可抑制 HCC 细胞的增殖,但不能抑制正常肝细胞的增殖。RMP 可显著抑制 SMMC-7721 和 HepG2 中的 HCC 细胞凋亡,但对正常肝细胞凋亡几乎没有影响。RMP 特征的机制依赖于 RMP 在 HCC 和肝细胞中诱导的凋亡因子的不同响应表达。过表达或耗尽 RMP 都会显著影响 HCC 细胞中凋亡因子的表达。然而,正常肝细胞对 RMP 调节凋亡的反应倾向于抵抗。在临床样本中,与 30 例 HCC 患者的配对非肿瘤组织相比,也观察到 HCC 中 RMP 的表达增加。RMP 在 HCC 和肝细胞之间的不同表达水平和不同反应表明,RMP 不仅可以作为 HCC 诊断的生物标志物,也可能成为 HCC 治疗的潜在靶点。