Research On The Molecular Mechanisms Of Hsa-miR-29c Modulating Proliferation, Invasion And Metastasis In Human Gallbladder Carcinoma

Background and purpose Gallbladder cancer(GBC) is the most common biliary tract malignancy and the seventh most common gastrointestinal cancer. The prognosis of advanced gallbladder carcinoma is very poor, the median survival of GBC patients is less than 1 year, which is due to early metastasis via lymphatic, perineural, and hematogenous routes, as well as direct invasion into the liver. Micro RNA(miRNA), a kind of recently discovered non-coding RNA, modulate target gene expression through sequence-specific binding to their m RNA targets, resulting in translational inhibition or m RNA degradation. A great number of evidences showed that miRNA take part in almost all the cellular biological process. However, whether miRNAs are involved in metastasis and progression of GBC remains obscure.Method To identify critical miRNA in GBC, miRNAs in GBC tissues and their corresponding non-tumor tissuses were screened using Agilent human miRNA array(V.19.0). The biological functions of miRNAs were intensively studies by transwell, immunoblot and immunohistochemical. Tumorigenicity and lung metastasis were further examined in nude mice.Result MiR-29c-5p were selected as the prominent inducers for GBCs. The ectopic expression of miR-29c-5p could reduce Epithelial-mesenchymal transition(EMT) and inhibit the proliferation as well as metastasis of GBC-SD cells in vitro and in vivo, through directly targeting 3‘UTR of SPOCK1. Conversely, the blockage of miR-29c-5p effectively restored the expression of SPOCK1.Conclusion MiR-29c-5p/SPOCK1 axis plays a pivotal role in the pathogenesis and worse prognosis of GBCs, which may serve as a potential therapeutic target in future.