Department of Ward 1 of Oncology, Hainan General Hospital, Haikou City, China.
Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Haikou City, China.
Kaohsiung J Med Sci. 2021 Apr;37(4):294-304. doi: 10.1002/kjm2.12323. Epub 2020 Nov 24.
Gallbladder carcinoma (GBC) commonly occurs in gastrointestinal malignancy and has the fifth highest mortality rate among gastrointestinal malignancy. Recently, miR-188-5p, a small noncoding RNA, has been implicated in various types of cancer such as nasopharyngeal carcinoma, oral squamous cell carcinoma, liver cancer, and prostate cancer. However, the effect of miR-188-5p on GBC remains unclear. Here, we demonstrated that miR-188-5p was downregulated in GBC tissues, and downregulation of miR-188-5p correlated with larger tumor size, lymph node metastasis, and extensive metastasis. In addition, the overall survival time of patients with higher miR-188-5p expression was significantly longer than that of patients with low-miR-188-5p expression. Moreover, downregulation of miR-188-5p promoted the proliferation, migration, and invasion of GBC cells, while its overexpression inhibited cell invasion and induced cell apoptosis, and arrested GBC growth in vivo. Importantly, miR-188-5p-dependent tumorigenesis was correlated with Wnt/β-catenin signaling and p-38/JNK signaling. In conclusion, miR-188-5p plays a direct role in GBC tumorigenesis. Our study suggests that miR-188-5p could serve as a novel diagnosis marker and therapeutic target in GBC.
胆囊癌（GBC）常发生于胃肠道恶性肿瘤，其死亡率在胃肠道恶性肿瘤中排名第五。最近，微小 RNA-188-5p（miR-188-5p）作为一种小的非编码 RNA，已被证实在多种癌症中发挥作用，如鼻咽癌、口腔鳞状细胞癌、肝癌和前列腺癌。然而，miR-188-5p 对 GBC 的影响尚不清楚。本研究表明，miR-188-5p 在 GBC 组织中呈下调表达，且 miR-188-5p 的下调与肿瘤体积较大、淋巴结转移和广泛转移有关。此外，miR-188-5p 高表达患者的总生存时间明显长于 miR-188-5p 低表达患者。此外，下调 miR-188-5p 促进 GBC 细胞的增殖、迁移和侵袭，而过表达 miR-188-5p 则抑制细胞侵袭并诱导细胞凋亡，从而在体内抑制 GBC 生长。重要的是，miR-188-5p 依赖性肿瘤发生与 Wnt/β-catenin 信号和 p38/JNK 信号有关。综上所述，miR-188-5p 直接参与 GBC 的肿瘤发生。本研究提示 miR-188-5p 可作为 GBC 的一种新型诊断标志物和治疗靶点。
