Diagnostic and therapeutic application of ribosomal proteins in gastrointestinal cancer

虽然核糖体蛋白是核糖体的主要组成部分，但最近的数据表明，它们除了核糖体和蛋白质生物合成外，还具有核糖体外的功能。在我们早期的研究中，我们发现核糖体蛋白L13 mRNA在仓鼠细胞中对DNA损伤的反应中上调。我们在这里报告，L13表达上调，在人类胃肠道肿瘤。我们还研究了L13对人类癌细胞的生物学作用。通过小干扰RNA（siRNA）敲低L13表达导致癌细胞生长急剧减弱，细胞周期显著G1和G2/M停滞。此外，L13 siRNA显著增强了细胞对某些DNA损伤剂的敏感性，并且一致地，L13过表达的细胞与亲本细胞相比表现出更大的化学抗性，表明L13表达与化学敏感性之间存在负相关。通过使用半定量RT-PCR，我们分析了L13在新鲜切除的胃癌、结直肠癌和肝癌组织中的表达。与邻近正常组织样品相比，在36个胃癌组织样品中的10个（28%）、46个结直肠癌组织样品中的19个（41%）和25个肝癌组织样品中的5个（20%）中观察到L13 mRNA表达上调。我们还发现L13基因的表达增加与胃癌的临床分期相关。本研究的结果表明，L13在某些胃肠道恶性肿瘤的进展中起着至关重要的作用。

Although ribosomal proteins are major components of ribosomes, recent data have shown them to have extraribosomal functions apart from the ribosome and protein biosynthesis. In our earlier study we showed that ribosomal protein L13 mRNA was upregulated in response to DNA damage in hamster cells. We report here that L13 expression is upregulated in human gastrointestinal cancers. We also examined the biological role of L13 on human cancer cells. Knocking down L13 expression by small interfering RNA (siRNA) resulted in drastic attenuation of cancer cell growth with significant G1 and G2/M arrest of the cell cycle. Moreover, L13 siRNA significantly enhanced the cellular sensitivity to certain DNA damaging agents and, concordantly, L13-overexpressing cells demonstrated greater chemoresistance compared to parent cells, suggesting an inverse correlation between L13 expression and chemosensitivity. By using semiquantitative RT-PCR, we analyzed expression of L13 in freshly resected cancer tissue of the stomach, colorectum, and liver. Upregulation of L13 mRNA expression was observed in 10 (28%) of 36 gastric, 19 (41%) of 46 colorectal, and 5 (20%) of 25 liver cancer tissue samples compared to adjacent normal tissue samples. We also found that increased expression of the L13 gene was correlated with clinical staging in gastric cancers. The results of this study suggest that L13 plays an essential role in the progression of some gastrointestinal malignancies.