Department of Oral Maxillofacial‑Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai 200011, P.R. China.
Oncol Rep. 2021 Mar;45(3):1182-1192. doi: 10.3892/or.2021.7940. Epub 2021 Jan 18.
Dysregulation of Rab proteins has been observed in various types of cancer. Ectopic expression of Rab31, a member of the Rab protein family, is involved in cancer development and progression. However, the specific role and potential molecular mechanism underlying the functions of Rab31 remain largely unknown. Therefore, the current study aimed to investigate the functions of Rab31 in the development of cancer. Human oral squamous cell carcinoma (OSCC) samples were examined to determine the expression profile of Rab31 and its association with the clinicopathological characteristics of patients with OSCC. Knockdown of Rab31 expression with short hairpin RNA was performed to analyze the functions of Rab31 in vitro and in vivo. The expression of Rab31 was significantly elevated in human OSCC samples compared with that in normal oral mucosal epithelial tissues, and high expression levels were associated with high pathological grades. Furthermore, positive expression of Rab31 was associated with a poor prognosis in patients with OSCC. In addition, knockdown of Rab31 expression suppressed OSCC cell proliferation and induced apoptosis compared with those in the control‑transfected cells, which may have been caused by downregulated cyclin D1 and survivin expression and upregulated B‑cell lymphoma 2 expression. The invasive ability of OSCC cells was also abrogated by Rab31 silencing compared with that in the control‑transfected cells, which was associated with downregulated N‑cadherin and matrix metalloproteinase‑9 expression levels and upregulated levels of E‑cadherin expression. Furthermore, silencing Rab31 in OSCC cell lines, when compared with the control‑transfected cells, significantly reduced tumor growth and inhibited the expression of survivin, Ki‑67 and N‑cadherin in vivo. By contrast, the expression levels of E‑cadherin were increased. Taken together, the results of the present study supported important roles for Rab31 in regulating OSCC cell proliferation, apoptosis and invasion and may facilitate the identification of a new therapeutic target for the treatment of OSCC.
Rab 蛋白的失调已在各种类型的癌症中观察到。Rab 蛋白家族成员 Rab31 的异位表达参与了癌症的发生和发展。然而，Rab31 功能的具体作用和潜在分子机制在很大程度上仍然未知。因此，本研究旨在探讨 Rab31 在癌症发展中的作用。检查人口腔鳞状细胞癌 (OSCC) 样本以确定 Rab31 的表达谱及其与 OSCC 患者临床病理特征的关系。使用短发夹 RNA 敲低 Rab31 表达以分析 Rab31 在体外和体内的功能。与正常口腔黏膜上皮组织相比，Rab31 在人 OSCC 样本中的表达明显升高，高表达水平与高病理分级相关。此外，Rab31 的阳性表达与 OSCC 患者的不良预后相关。此外，与对照转染细胞相比，Rab31 表达的敲低抑制了 OSCC 细胞的增殖并诱导了细胞凋亡，这可能是由于 cyclin D1 和 survivin 表达下调以及 B 细胞淋巴瘤 2 表达上调所致。与对照转染细胞相比，Rab31 沉默还削弱了 OSCC 细胞的侵袭能力，这与 N-钙粘蛋白和基质金属蛋白酶-9 表达水平下调以及 E-钙粘蛋白表达水平上调有关。此外，与对照转染细胞相比，沉默 OSCC 细胞系中的 Rab31 显著降低了肿瘤生长并抑制了体内 survivin、Ki-67 和 N-钙粘蛋白的表达。相比之下，E-钙粘蛋白的表达水平增加。总之，本研究的结果支持 Rab31 在调节 OSCC 细胞增殖、凋亡和侵袭中的重要作用，并可能为 OSCC 的治疗提供新的治疗靶点。
