Abstract
BackgroundCholangiocarcinoma is a common malignant tumor of digestive system. LncRNA metallothionein 1 J, pseudogene (MT1JP) has been reported to play tumor-suppressing roles in multiple cancers. However, its effect on cholangiocarcinoma has not been evaluated.MethodsThe expression of MT1JP in intrahepatic cholangiocarcinoma specimens and paired para-carcinoma tissues were detected by real-time PCR. The overexpression plasmid and siRNA of MT1JP were transfected into intrahepatic cholangiocarcinoma cells to change the expression levels of MT1JP. CCK-8, flow cytometry and transwell assays were performed to measure proliferation, cell cycle transition, apoptosis, migration and invasion. Dual-luciferase reporter assay, real-time PCR and western blot were carried out to screen the miRNA bound by MT1JP. In addition, xenograft experiment was used to determine the tumorigenesis of cholangiocarcinoma cells in nude mice.ResultsMT1JP was downregulated in intrahepatic cholangiocarcinoma specimens, and its expression was related with TNM stage and lymph node metastasis. Overexpression of MT1JP inhibited proliferation, cell cycle transition, migration and invasion, and induced apoptosis in intrahepatic cholangiocarcinoma cells. The knockdown of MT1JP led to opposite results. MT1JP bound to miR-18a-5p to facilitate the expression of fructose-1,6-bisphosphatase 1 (FBP1). MiR-18a-5p was increased in intrahepatic cholangiocarcinoma samples, and its expression was negatively correlated with that of MT1JP. In addition, MT1JP also suppressed tumorigenesis in nude mice.ConclusionsMT1JP alleviated proliferation, migration and invasion, and induced apoptosis in cholangiocarcinoma cells by regulating miR-18a-5p/FBP1 axis. These findings may provide novel insights for clinical diagnosis and treatment of cholangiocarcinoma.
Highlights
Cholangiocarcinoma is a common malignant tumor of digestive system
MT1JP was downregulated in cholangiocarcinoma specimens MT1JP gene is located in chr16:56635793–56,637,086, and miR-18a gene is located in chr13:91350751–91,350, 721, as shown in Fig. 1a and b
According to TCGA database, MT1JP and FBP1 were downregulated and miR-18a-5p was upregulated in clinical cholangiocarcinoma tissues (Fig. 1c)
Summary
Cholangiocarcinoma is a common malignant tumor of digestive system. Its effect on cholangiocarcinoma has not been evaluated. Cholangiocarcinoma is a common malignant tumor of digestive system, and the overall incidence of cholangiocarcinoma has progressively increased worldwide over the past decades [1]. Surgery resection is still the only effective treatment for cholangiocarcinoma. As the anatomical concealment of bile duct, most patients with early stage are asymptomatic, and the early diagnose is difficult [5]. Most patients are diagnosed at an advanced stage with mestastasis [6]. For patients with advanced-stage or unresectable cholangiocarcinoma, the available systemic therapies are of limited effectiveness: the median overall survival with the current standard-of-care chemotherapy regimen is less than one year [7]. The early diagnosis is vital for outcome of cholangiocarcinoma patients
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