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Kaohsiung J Med Sci ; 37(4): 294-304, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33236530

ABSTRACT

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/ß-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.


Subject(s)
Gallbladder Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Glycoproteins/genetics , MicroRNAs/genetics , Smad2 Protein/genetics , Wnt Proteins/genetics , Aged , Animals , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Survival , Female , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/surgery , Glycoproteins/metabolism , Humans , Lymphatic Metastasis , Male , Mice , MicroRNAs/metabolism , Middle Aged , Neoplasm Staging , Signal Transduction , Smad2 Protein/metabolism , Survival Analysis , Tumor Burden , Wnt Proteins/metabolism , Xenograft Model Antitumor Assays
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