Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241000, P.R. China.
Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215006, P.R. China.
Oncol Rep. 2019 May;41(5):2717-2728. doi: 10.3892/or.2019.7071. Epub 2019 Mar 15.
Colorectal carcinoma (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer‑related deaths in the US. Recently, Rab1A has been reported to be an activator of mTORC1 and p‑S6K1, which is downstream of mTORC1. However, the association between Rab1A and p‑S6K1 in CRC remains elusive. In the present study, we first demonstrated that Rab1A was overexpressed in CRC tissues and Rab1A overexpression was positively related to lymph node invasion, degree of differentiation, venous invasion and tumor‑node‑metastasis (TNM) stage. In both TNM stage I‑II and III‑IV patients, Rab1A‑positive patients had a shorter survival time than Rab1A‑negative patients. Furthermore, in univariate and multivariate analyses, only Rab1A expression was verified as an independent prognostic factor for survival in CRC patients. The level of p‑S6K1 was markedly high in CRC tissues and Rab1A expression level had a positive association with p‑S6K1 level. In addition, high levels of both Rab1A and p‑S6K1 were associated with a poorer prognosis compared with low expression of either Rab1A or p‑S6K1 level. Moreover, high levels of both Rab1A and p‑S6K1 were associated with a poorer prognosis than patients with high levels of either Rab1A or p‑S6K1 alone. Finally, knockdown of Rab1A expression inhibited migration and proliferation of SW480 and HCT116 cell lines by targeting regulation of p‑S6K1. Thus, our findings indicate that Rab1A plays an important role in CRC and may provide a therapeutic target for CRC, particularly for mTORC1‑targeted therapy‑resistant cancers.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一，也是美国癌症相关死亡的第二大主要原因。最近，Rab1A 被报道为 mTORC1 和 p-S6K1 的激活剂，而 p-S6K1 是 mTORC1 的下游靶点。然而，Rab1A 与 CRC 中的 p-S6K1 之间的关联仍不清楚。在本研究中，我们首先证明 Rab1A 在 CRC 组织中过表达，Rab1A 过表达与淋巴结侵犯、分化程度、静脉侵犯和肿瘤-淋巴结-转移（TNM）分期呈正相关。在 TNM 分期 I-II 期和 III-IV 期患者中，Rab1A 阳性患者的生存时间短于 Rab1A 阴性患者。此外，在单因素和多因素分析中，只有 Rab1A 表达被证实是 CRC 患者生存的独立预后因素。CRC 组织中 p-S6K1 的水平明显升高，Rab1A 表达水平与 p-S6K1 水平呈正相关。此外，与 Rab1A 或 p-S6K1 水平低表达相比，高表达的 Rab1A 和 p-S6K1 与预后较差相关。此外，与单独高表达 Rab1A 或 p-S6K1 的患者相比，高表达的 Rab1A 和 p-S6K1 与预后较差相关。最后，通过靶向调节 p-S6K1，Rab1A 表达的敲低抑制了 SW480 和 HCT116 细胞系的迁移和增殖。因此，我们的研究结果表明，Rab1A 在 CRC 中发挥重要作用，可能为 CRC 提供治疗靶点，特别是对 mTORC1 靶向治疗耐药的癌症。
