Department of Emergency Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Department of Pathology, The Second People's Hospital of Hefei, Hefei, Anhui 230011, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7277-7286. doi: 10.3892/mmr.2017.7541. Epub 2017 Sep 20.
Gastric cancer is one of the most common cancers and the second leading cause of cancer‑associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c‑Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T‑cell lymphoma. c‑Maf inducing protein (CMIP) is involved in the c‑Maf signaling pathway, which was reported to serve an important role in human minimal change nephrotic syndrome and in human reading and language related behavior. However, the relationship between CMIP and human gastric cancer has not yet been reported. In the present study, CMIP protein levels in gastric cancer tissues and cells were measured using immunohistochemistry and western blot analysis; the expression of CMIP protein was significantly higher in gastric cancer tissues compared with normal gastric tissues. Expression was positively associated with poorer clinical parameters, relapse‑free survival and overall survival. Furthermore, using cell counting, Cell Counting Kit‑8, colony formation, wound healing and Transwell assays, together with flow cytometry, CMIP depletion by RNA interference was observed to reduce the capacity of gastric cancer cells to proliferate and migrate in vitro. Furthermore, the upstream and downstream genes of CMIP were analyzed by luciferase reporter assay and reverse transcription quantitative polymerase chain reaction, which indicated that CMIP was a direct target of miR‑101‑3p. In addition, CMIP knockdown was observed to result in the downregulation of MDM2 and mitogen activated protein kinase (MAPK) expression at the mRNA level. In conclusion, CMIP demonstrated an oncogenic role in human gastric cancer cells. Furthermore, microRNA‑101‑3p, MDM2 and MAPK were involved in the CMIP signaling pathway in gastric cancer. CMIP could be a novel target for further investigation in the clinical therapeutic management of gastric cancer.
胃癌是最常见的癌症之一，也是全球癌症相关死亡的第二大主要原因。复发、转移和对药物治疗的耐药性是晚期胃癌患者生存的主要障碍。进一步研究相关的分子机制将改善胃癌的治疗选择。在之前的一项研究中，c-Maf 被发现是禽类 AS42 逆转录病毒转导的致癌基因，并且在多发性骨髓瘤和血管免疫母细胞性 T 细胞淋巴瘤中过表达。c-Maf 诱导蛋白（CMIP）参与 c-Maf 信号通路，该通路被报道在人类微小病变性肾病综合征和人类阅读和语言相关行为中发挥重要作用。然而，CMIP 与人类胃癌之间的关系尚未报道。在本研究中，通过免疫组织化学和 Western blot 分析检测了胃癌组织和细胞中的 CMIP 蛋白水平；与正常胃组织相比，胃癌组织中 CMIP 蛋白的表达显著升高。表达与较差的临床参数、无复发生存和总生存呈正相关。此外，通过细胞计数、Cell Counting Kit-8、集落形成、划痕愈合和 Transwell 测定以及流式细胞术观察到，通过 RNA 干扰耗尽 CMIP 可降低体外胃癌细胞的增殖和迁移能力。此外，通过荧光素酶报告基因测定和逆转录定量聚合酶链反应分析了 CMIP 的上下游基因，表明 CMIP 是 miR-101-3p 的直接靶基因。此外，观察到 CMIP 敲低导致 MDM2 和丝裂原激活蛋白激酶（MAPK）在 mRNA 水平的表达下调。总之，CMIP 在人类胃癌细胞中表现出致癌作用。此外，microRNA-101-3p、MDM2 和 MAPK 参与了胃癌中的 CMIP 信号通路。CMIP 可能是胃癌临床治疗管理中进一步研究的新靶点。
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