Tang Yunyun, Liu Xiaoping, Su Bo, Zhang Zhiwei, Zeng Xi, Lei Yanping, Shan Jian, Wu Yongjun, Tang Hailin, Su Qi
Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
Sun Yat‑Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
Mol Med Rep. 2015 Jan;11(1):454-60. doi: 10.3892/mmr.2014.2682. Epub 2014 Oct 16.
microRNA (miR)-22 has been reported to be downregulated in hepatocellular, lung, colorectal, ovarian and breast cancer, acting as a tumor suppressor. The present study investigated the potential effects of miR-22 on gastric cancer invasion and metastasis and the molecular mechanism. miR-22 expression was examined in tumor tissues of in 89 gastric cancer patients by in situ hybridization (ISH) analysis. Additionally, the association between miR-22 levels and clinicopathological parameters was analyzed. A luciferase assay was conducted for target identification. The ability of invasion and metastasis of gastric cancer cells in vitro and in vivo was evaluated by cell migration and invasion assays and in a xenograft model. The results showed that miR-22 was downregulated in the gastric cancer specimens and significantly correlated with the advanced clinical stage and lymph node metastasis. In addition, metadherin (MTDH) was shown to be a direct target of miR-22 and the expression of MTDH was inversely correlated with miR-22 expression in gastric cancer. Ectopic expression of miR-22 suppressed cell invasion and metastasis in vitro and in vivo. The present study suggested that miR-22 may be a valuable prognostic factor in gastric cancer. miR-22 inhibited gastric cancer cell invasion and metastasis by directly targeting MTDH. The novel miR-22/MTDH link confirmed in the present study provided a novel, potential therapeutic target for the treatment of gastric cancer.
据报道，微小RNA（miR）-22在肝细胞癌、肺癌、结直肠癌、卵巢癌和乳腺癌中表达下调，起到肿瘤抑制作用。本研究调查了miR-22对胃癌侵袭和转移的潜在影响及其分子机制。通过原位杂交（ISH）分析检测了89例胃癌患者肿瘤组织中miR-22的表达。此外，分析了miR-22水平与临床病理参数之间的关联。进行荧光素酶测定以鉴定靶点。通过细胞迁移和侵袭试验以及异种移植模型评估胃癌细胞在体外和体内的侵袭和转移能力。结果显示，miR-22在胃癌标本中表达下调，且与临床晚期和淋巴结转移显著相关。此外，黏附素（MTDH）被证明是miR-22的直接靶点，且在胃癌中MTDH的表达与miR-22的表达呈负相关。miR-22的异位表达在体外和体内均抑制细胞侵袭和转移。本研究表明，miR-22可能是胃癌中一个有价值的预后因素。miR-22通过直接靶向MTDH抑制胃癌细胞的侵袭和转移。本研究中证实的新型miR-22/MTDH联系为胃癌治疗提供了一个新的潜在治疗靶点。
