Department of General Surgery, Nanjing Medical University, Affiliated Suzhou Hospital, Gusu, Suzhou, Jiangsu 215000, P.R. China.
Oncol Rep. 2017 Nov;38(5):2967-2974. doi: 10.3892/or.2017.5957. Epub 2017 Sep 18.
RAB34, a protein belonging to the RAB family, is involved in protein transport, repositioning of lysosomes and activation of micropinocytosis. However, few studies have reported its function in human epithelial cancers. Immunohistochemistry (IHC) and western blotting were used to detect expression of RAB34 at the tissue and cell levels. Cell Counting Kit-8 (CCK-8), EDU assay and flow cytometry were used for analyzing cell proliferation. Transwell and scratch wound healing assays were used for assessing cell migration ability. Western blotting was used for detecting expression of E-cadherin and N-cadherin. In the present study, we found that both DNA copy and protein level of RAB34 were upregulating in human hepatocellular carcinoma (HCC) tissues when compared with that in adjacent tissues. Analysis of the correlation between RAB34 expression and clinicopathological features showed that patients with overexpression of RAB34 consistently had large tumor size, vessel invasion and poor tumor grade. Furthermore, overall survival analysis showed that patients with upregulated expression of RAB34 were associated with poor prognosis. Moreover, cell function experiments showed that suppression of RAB34 led to a lower proliferation rate and migration ability. In addition, this phenomenon may be attributed to cell cycle phase G1 arrest and mesenchymal-epithelial transition under condition of RAB34 suppression. The present study demonstrated that RAB34 plays an important role in the initiation and progression of HCC. Our results suggest a new therapeutic target for the clinical treatment of HCC.
RAB34 是 RAB 家族的一种蛋白，参与蛋白质运输、溶酶体重定位和微绒毛内吞作用的激活。然而，目前关于 RAB34 在人类上皮性肿瘤中的作用的研究较少。本研究采用免疫组织化学（IHC）和蛋白质印迹法检测 RAB34 在组织和细胞水平的表达。通过细胞计数试剂盒（CCK-8）、EDU 检测和流式细胞术分析细胞增殖。通过 Transwell 和划痕愈合实验评估细胞迁移能力。通过蛋白质印迹法检测 E-钙黏蛋白和 N-钙黏蛋白的表达。本研究发现，与相邻组织相比，人肝癌（HCC）组织中 RAB34 的 DNA 拷贝数和蛋白水平均上调。分析 RAB34 表达与临床病理特征之间的相关性表明，RAB34 过表达的患者肿瘤体积较大、血管侵袭和肿瘤分级较差。此外，总生存分析表明，RAB34 表达上调的患者预后不良。此外，细胞功能实验表明，抑制 RAB34 可导致增殖率和迁移能力降低。此外，这种现象可能归因于 RAB34 抑制时细胞周期 G1 期停滞和上皮间质转化。本研究表明，RAB34 在 HCC 的发生和发展中起重要作用。我们的研究结果为 HCC 的临床治疗提供了新的治疗靶点。
