Abstract
Gallbladder carcinoma (GBC), the most common malignant tumour of the bile duct, is highly aggressive and has a poor prognosis. MicroRNA-30a-5p (miR-30a-5p) is an important tumour suppressor that participates in many aspects of carcinogenesis and cancer development. However, the role of miR-30a-5p in GBC development remains to be determined, as do the mechanisms underlying its effects in GBC. Using samples collected from 42 subjects with gallbladder carcinoma (GBC), we showed decreased miR-30a-5p expression in the primary lesions vs. non-tumour adjacent tissues (NATs). Decreased miR-30a-5p was associated with shorter disease-free survival (DFS) and overall survival (OS). Inhibiting miR-30a-5p expression in 2 representative GBC cell lines (GBC-SD and NOZ) increased cell proliferation, migration, invasiveness, as well as β-catenin nuclear translocation, vice versa. In nude mice, NOZ cells transfected with miR-30a-5p mimics grew slower (vs. miR-NC) upon subcutaneous inoculation, and had lower rate of hepatic metastasis upon spleen inoculation. Dual luciferase assay confirmed that E2F transcription factor 7 (E2F7) was a direct target of miR-30a-5p and antagonized the effects induced by miR-30a-5p downregulation in GBC cells. MiR-30a-5p attenuates the EMT and metastasis in GBC cells by targeting E2F7, suggesting miR-30a-5p is a tumour suppressor that may serve as a novel potential prognostic biomarker or molecular therapeutic target for GBC.
Highlights
Gallbladder carcinoma (GBC) have not significantly improved because the diseaseGBC is the most common and aggressive malignancy of metastasizes early and its diagnosis is often delayed[3].the bile duct, and the worldwide incidence of the disease is increasing annually[1]
We found that the transcription factor E2F transcription factor 7 (E2F7) is a novel, direct target of miR30a-5p in GBC and that an inverse correlation exists between miR-30a-5p and E2F7 expression messenger RNAs (mRNAs) levels in GBC tissues
Numerous studies have unveiled a number of miRNA signatures in GBC4, 19, 20, but the exact role of miRNA dysregulation in the pathogenesis of GBC has remained unclear
Summary
GBC have not significantly improved because the diseaseGBC is the most common and aggressive malignancy of metastasizes early and its diagnosis is often delayed[3].the bile duct, and the worldwide incidence of the disease is increasing annually[1]. GBC have not significantly improved because the disease. The prognosis of GBC is very poor, as the 5-year survival rate for patients with the disease is
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