Exosomes secreted by chronic hepatitis B patients with PNALT and liver inflammation grade ≥ A2 promoted the progression of liver cancer by transferring miR-25-3p to inhibit the co-expression of TCF21 and HHIP.

OBJECTIVES:The current study aimed to investigate the mechanism by which exosomes secreted by CHB patients with and liver inflammation grade (≥A2) affected the development of liver cancer. MATERIALS AND METHODS:Gene expression was assessed by RT-PCR, Western blotting and immunohistochemistry. CCK-8, colony formation, transwell, scratch-wound and flow cytometry assays were used to detect cell viability, proliferation, apoptosis and metastasis. The interaction of TCF21 and HHIP was assessed by co-immunoprecipitation assay. Luciferase reporter was used to detect the combination of TCF21/HHIP and miR-25-3p. Xenograft studies in nude mice manifested tumour growth ability of miR-25-3p. Bioinformatics analyses were conducted using TargetScan, EVmiRNA, TCGA, GEO, DAVID, COEXPEDIA, UALCAN, UCSC and the Human Protein Atlas (≥A2) promoted the proliferation and metastasis of HepG2.2.15 cells. miR-25-3p was upregulated in (≥A2). miR-25-3p overexpression promoted cell proliferation and metastasis and was related to poor survival in patients with (≥A2). The cell proliferation- and metastasis-promoting functions of CHB-duanyu1535LT-Exo (≥A2) were abolished by miR-25-3p inhibitors. TCF21 directly interacted with HHIP. Inhibition of TCF21 or HHIP promoted cell proliferation and metastasis. Knockdown of TCF21 or HHIP counteracted the effects of CHB-duanyu1535LT-Exo (≥A2) containing miR-25-3p inhibitor on cell proliferation, metastasis and the expression of Ki67, E-cadherin and caspase-3/-9. CONCLUSIONS:Transfer of miR-25-3p by CHB-duanyu1535LT-Exo promoted the development of liver cancer by inhibiting the co-expression of TCF21 and HHIP.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}