Abstract
BackgroundGallbladder cancer (GBC) is a malignant cancer with poor prognosis. Evidences have shown that miRNAs are closely related to the occurrence of GBC; thus, we aimed to explore miRNAs, which plays an important role in the occurrence and development of GBC.MethodsMicroarray analysis was performed to investigate the differentially expressed miRNAs between five non-neoplastic gallbladder tissues (normal tissues) and five gallbladder tumor tissues (tumor tissues). RT-qPCR was performed to detect the level of miR-181b-5p in cells, and CCK-8 was performed to detect cell viability. Then, glucose assay kit or lactic acid assay kit was performed to detect the level of glucose consumption or lactate production. Next, transwell and wound healing assays were used to assess cell migration. In addition, dual-luciferase reporter assay was used to verify the relationship between miR-181b-5p and PDHX. At last, Western blotting was performed to determine the protein level of PDHX.ResultsMicroarray analysis suggested miR-181b-5p was significantly upregulated in GBC tumor tissue. KEGG analysis for the protein targets of miR-181b-5p indicates a close relationship existed between miR-181b-5p and glycolysis. In addition, the level of miR-181b-5p was notably increased in GBC-SD or G415 cells, compared with HIBEpiC cells. GBC cell viability was significantly decreased under hypoxia, and these decreases were exacerbated by miR-181b-5p antagomir. Moreover, glucose consumption or lactate production of GBC cells was significantly upregulated under hypoxia, whereas these increases were completely revered by miR-181b-5p antagomir. Further investigation revealed that PDHX was a direct target of miR-181b-5p.ConclusionIn this study, downregulation of miR-181b-5p inhibits the viability, migration, and glycolysis of GBC by upregulating PDHX under hypoxia. This finding suggested that miR-181b-5p might be considered as a novel therapeutic target for the treatment of GBC.
Highlights
Gallbladder carcinoma (GBC) is a malignant tumor originating from the epithelial cells of gallbladder mucosa [1, 2]
Because miR-181b-5p was reported to be closely related to the occurrence and development of GBC [16], miR-181b-5p was selected for further investigation
We firstly confirm the expression of miR-181b-5p in GBC cancer using with RTqPCR
Summary
Gallbladder carcinoma (GBC) is a malignant tumor originating from the epithelial cells of gallbladder mucosa [1, 2]. The main causes of GBC include gallbladder stones, specific types of gallbladder lesions, bacterial infections, and genetic factors [4]. GBC can be divided into five stages, according to the severity of the patient’s condition [5]. Treatment can be divided into drug therapy, surgery, radiation therapy, and chemical therapy based on the stage of GBC [6]. Most patients with GBC were diagnosed at a late stage and had a poor prognosis [7]. Piehler et al reported that the 5-year survival rate for patients with GBC is only 4.1% [8, 9]. Gallbladder cancer (GBC) is a malignant cancer with poor prognosis. Evidences have shown that miRNAs are closely related to the occurrence of GBC; we aimed to explore miRNAs, which plays an important role in the occurrence and development of GBC
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